Using multiple diagnostic parameters for predicting heart failure events

ABSTRACT

Techniques for using multiple physiological parameters to provide an early warning for worsening heart failure are described. A medical device monitors a primary diagnostic parameter that is indicative of worsening heart failure, such as intrathoracic impedance or pressure, and one or more secondary diagnostic parameters. The medical device detects worsening heart failure in the patient based on the primary diagnostic parameter when an index that is changed over time based on the primary diagnostic parameter value is outside a range of values, termed the threshold zone. When the index is within the threshold zone, the medical device detects worsening heart failure in the patient based on the one or more secondary diagnostic parameters. Upon detecting worsening heart failure, the medical device may, for example, provide an alert that enables the patient to seek medical attention before experiencing a heart failure event.

TECHNICAL FIELD

The invention relates to medical devices and, more particularly, devicesfor the diagnosis of worsening heart failure and treatment of relatedailments.

BACKGROUND

A variety of medical devices have been used or proposed for use todeliver a therapy to and/or monitor a physiological condition ofpatients. As examples, such medical devices may deliver therapy and/ormonitor conditions associated with the heart, muscle, nerve, brain,stomach or other organs or tissue. Medical devices that deliver therapyinclude medical devices that deliver one or both of electricalstimulation or a therapeutic agent to the patient. Some medical devicesare implantable medical devices (IMDs) that are implanted within thepatient.

Some medical devices have been used or proposed for use to monitor heartfailure or to detect heart failure events. Typically, such medicaldevices have been implantable and, in many cases, have been cardiacpacemakers, cardioverters and/or defibrillators with added heart failuremonitoring functionality. In some cases, such medical devices havemonitored heart failure by monitoring intrathoracic impedance, which mayprovide a good indication of the level of edema in patients. While edemais a sign of many other conditions it is also a sign of worsening heartfailure. Worsening heart failure may result in cardiac chamber dilation,increased pulmonary blood volume, and fluid retention in the lungs—allof which contribute to a decrease in intrathoracic impedance. Otherdiagnostic parameters, such as heart rate variability, have beenproposed for use in such devices to identify worsening heart failure orheart failure events.

Generally, the first indication that a physician would have of theoccurrence of edema in a patient is not until it becomes a physicalmanifestation with swelling or breathing difficulties so overwhelming asto be noticed by the patient who then proceeds to be examined by aphysician. This is undesirable since hospitalization at such a timewould likely be required for a heart failure patient. Accordingly,medical devices have been used to monitor impedance in patients andprovide an alert to the patient to seek medical treatment prior to theonset of worsening heart failure with symptoms, such as edema, thatrequire hospitalization.

SUMMARY

This disclosure describes techniques for using multiple diagnosticparameters to provide an early warning for worsening heart failure. Amedical device monitors a primary diagnostic parameter and one or moresecondary diagnostic parameters indicative of worsening heart failure inthe patient. In some examples, the primary diagnostic parameterindicates a level of pulmonary edema, increased ventricular fillingpressure, or other morbidities associated with worsening heart failure.Examples of primary diagnostic parameters include intrathoracicimpedance or a cardiovascular pressure. The medical device detectsworsening heart failure in the patient based on the primary diagnosticparameter when an index that is changed over time based on the primarydiagnostic parameter value is outside a range of values, termed thethreshold zone. When the index is within the threshold zone, the medicaldevice detects worsening heart failure in the patient based on the oneor more secondary diagnostic parameters.

When the index is within the threshold zone, the medical device may lookto one or more secondary diagnostic parameters to corroborate theindication of worsening heart failure provided by the primary diagnosticparameter. In this manner, the medical device may more accuratelyidentify instances of worsening heart failure. Upon detecting worseningheart failure, the medical device may, for example, provide an alertthat enables the patient to seek medical attention before experiencing aheart failure event. The alert may be communicated directly to thepatient or to the clinician through a variety of methods, includingaudible tones, handheld devices and automatic telemetry to computerizedcommunication network.

The device may be a purely diagnostic device or may be a combinationdevice that monitors diagnostic parameters and delivers therapy. In someembodiments, the medical device may be configured as an implantablemedical device (IMD) or an external device. In some cases, an IMD may beimplanted subcutaneously. In other examples, a system may include an IMDand a programmer or other external device in communication with the IMD.In such embodiments, the external device may process data received fromthe IMD to detect worsening heart failure in the patient and/or providean alert if worsening heart failure is detected.

In operation, the medical device monitors the primary diagnosticparameter to obtain measured values. The medical device alsoperiodically changes a value of an index that indicates worsening heartfailure based on the measured values of the primary diagnosticparameter, e.g., based on whether the values of the primary diagnosticparameter are increasing or decreasing. The secondary diagnosticparameter value may not be considered in determining whether to providean alert of worsening heart failure when the index is outside thethreshold zone. If the index is greater than an upper threshold value ofthe threshold zone, worsening heart failure may be detected and an alertmay be provided to the patient. If the index is less than a lowerthreshold value of the threshold zone, worsening heart failure is notdetected and the medical device continues to monitor the primarydiagnostic parameter. However, when the index is within the thresholdzone, the secondary diagnostic parameter value is used to detectworsening heart failure in the patient. Worsening heart failure isdetected when the secondary diagnostic parameter satisfies acorresponding condition.

In some examples, the secondary diagnostic parameters are monitoredprior to the index being within the threshold zone. The secondarydiagnostic parameters may be monitored prior to the index being in thethreshold zone to provide information regarding trends in secondarydiagnostic parameters that may be used to determine whether thesecondary diagnostic parameters indicate worsening heart failure whenthe index is within the threshold zone. For example, some devices orsystems may begin monitoring one or more secondary diagnostic parameterswhen the index is greater than a secondary diagnostic parameterthreshold. The secondary diagnostic parameter threshold may be less thanthe lower threshold of the threshold zone, such that the secondarydiagnostic parameters may be monitored prior to the index entering thethreshold zone. In some examples, the device or system may monitor oneor more secondary diagnostic parameters within an observation windowdefined by the secondary diagnostic parameter threshold and the upperthreshold of the index.

Example secondary diagnostic parameters include atrial fibrillation(AF), heart rate during AF, ventricular fibrillation (VF), heart rateduring VF, atrial tachyarrhythmia (AT), heart rate during AT,ventricular tachyarrhythmia (VT), heart rate during VT, activity level,heart rate variability, night heart rate, difference between day heartrate and night heart rate, heart rate turbulence, heart ratedeceleration capacity, respiratory rate, baroreflex sensitivity,percentage of cardiac resynchronization therapy (CRT) pacing, metrics ofrenal function, weight, blood pressure, symptoms entered by the patientvia a programmer, and patient history, such as medication history, orhistory of heart failure hospitalizations. In one example, the medicaldevice may monitor one secondary diagnostic parameter and detectworsening heart failure in the patient based on the secondary diagnosticparameter when the index is within the threshold zone. In anotherexample, the device may monitor two or more secondary diagnosticparameters and detect worsening heart failure in the patient when atleast one of the secondary diagnostic parameters satisfies acorresponding condition. In another example, the device may monitor twoor more secondary diagnostic parameters and detect worsening heartfailure in the patient when a chosen combination of the secondarydiagnostic parameters satisfies a corresponding condition.

The threshold zone may be static or dynamic. For example, the thresholdzone may change as a function of time or based on knowledge of thecondition of the patient. In particular, the threshold zone mayautomatically change as a function of time. In contrast, a clinician orother authorized user may use an external programmer to manually changethe threshold zone based on knowledge of the condition of the patient.

In one example, the disclosure provides a method comprising monitoringat least one primary diagnostic parameter and at least one secondarydiagnostic parameter of a patient, wherein the primary and secondarydiagnostic parameters are associated with worsening heart failure,changing an index value over time based on the primary diagnosticparameter, wherein the index value indicates worsening heart failure ofthe patient, determining whether worsening heart failure is detected inthe patient based on the index when the index is outside of a thresholdzone defined by a lower threshold and an upper threshold, anddetermining whether worsening heart failure is detected in the patientbased on the secondary diagnostic parameter when the index is inside thethreshold zone.

In another example, the disclosure provides a system comprising at leastone sensor and a processor. The processor monitors at least one primarydiagnostic parameter and at least one secondary diagnostic parameter ofa patient based on at least one signal from the at least one sensor,wherein the primary and secondary diagnostic parameters are associatedwith worsening heart failure of the patient, changes an index value overtime based on the primary diagnostic parameter, wherein the indexindicates worsening heart failure in the patient, determines whetherworsening heart failure is detected in the patient based on the indexwhen the index is outside of a threshold zone defined by a lowerthreshold and an upper threshold, and determines whether worsening heartfailure is detected in the patient based on the secondary diagnosticparameter when the index is inside the threshold zone.

In another example, the disclosure provides a computer-readable mediumcomprising instructions that cause a processor to monitor at least oneprimary diagnostic parameter and at least one secondary diagnosticparameter of a patient, wherein the primary and secondary diagnosticparameters are associated with worsening heart failure, change an indexvalue over time based on the primary diagnostic parameter, wherein theindex indicates worsening heart failure in the patient, determinewhether worsening heart failure is detected in the patient based on theindex when the index is outside of an threshold zone defined by a lowerthreshold and an upper threshold, and determine whether worsening heartfailure is detected in the patient based on the secondary diagnosticparameter when the index is inside the threshold zone.

In another example, the disclosure provides a system comprising meansfor monitoring at least one primary diagnostic parameter and at leastone secondary diagnostic parameter of a patient, wherein the primary andsecondary diagnostic parameters are associated with worsening heartfailure, means for changing an index value over time based on theprimary diagnostic parameter, wherein the index indicates worseningheart failure in the patient, means for determining whether worseningheart failure is detected in the patient based on the index when theindex is outside of a threshold zone defined by a lower threshold and anupper threshold, and means for determining whether worsening heartfailure is detected in the patient based on the secondary diagnosticparameter when the index is inside the threshold zone.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a conceptual diagram illustrating an example system thatdetects worsening heart failure using multiple diagnostic parameters.

FIG. 2 is a conceptual diagram illustrating the implantable medicaldevice (IMD) and leads of the system shown in FIG. 1 in greater detail.

FIG. 3 is a functional block illustrating an example configuration ofthe IMD shown in FIG. 1.

FIG. 4 is a functional block diagram illustrating an exampleconfiguration of the programmer shown in FIG. 1.

FIG. 5 is a functional block diagram illustrating an exampleconfiguration of a diagnostic unit shown in FIG. 3 and FIG. 4.

FIG. 6 is functional block diagram illustrating an example configurationof an impedance analysis unit shown in FIG. 5.

FIG. 7 is a functional block diagram illustrating an example of thefunctionality of a secondary diagnostic parameter unit shown in FIG. 5.

FIG. 8 is a functional block diagram illustrating an exampleconfiguration of a diagnostic module shown in FIG. 5.

FIG. 9 is a flow diagram illustrating an example method that may beperformed by the IMD or programmer shown in FIG. 1 to detect worseningheart failure in a patient.

FIG. 10 is a flow diagram illustrating an example method for monitoringa primary diagnostic parameter.

FIGS. 11-15 are flow diagrams illustrating example methods formonitoring secondary diagnostic parameters.

FIG. 16 is a graph illustrating an example of a fluid index thatincrements over time relative to an example threshold zone.

FIG. 17 is a block diagram illustrating an example system that includesan external device, such as a server, and one or more computing devicesthat are coupled to the IMD and programmer shown in FIG. 1 via anetwork.

DETAILED DESCRIPTION

FIG. 1 is a conceptual diagram illustrating an example system 10 thatmay be used to detect worsening heart failure in patient 14 usingmultiple diagnostic parameters. Generally, system 10 generates an alertin response to detecting worsening heart failure so that patient 14 canseek appropriate treatment before experiencing a heart failurehospitalization (HFH) event. Patient 14 ordinarily, but not necessarily,will be a human.

System 10 includes implantable medical device (IMD) 16, which is coupledto leads 18, 20, and 22, an electrode 34 located on the can of IMD 16,and a programmer 24. In some examples, IMD 16 may be a purely diagnosticdevice that monitors multiple diagnostic parameters associated withheart failure. In other examples, IMD 16 may additionally operate as atherapy delivery device to deliver electrical signals to heart 12 viaone or more of leads 18, 20, and 22, such as an implantable pacemaker, acardioverter, and/or defibrillator. In some examples, IMD 16 may operateas a drug delivery device that delivers therapeutic substances topatient 14 via catheters (not shown), or as a combination therapy devicethat delivers both electrical signals and therapeutic substances.Moreover, IMD 16 is not limited to devices implanted as shown in FIG. 1.As an example, IMD 16 may be implanted subcutaneously in patient 14, ormay be an entirely external device with leads attached to the skin ofpatient 14 or implanted percutaneously in patient 14. In some examples,IMD 16 need not include leads, but may include a plurality ofelectrodes, like electrode 34, on the housing of IMD 16.

In general, IMD 16 monitors a primary diagnostic parameter that isindicative of fluid accumulation and one or more secondary diagnosticparameters. In particular, IMD 16 may monitor the primary diagnosticparameter and the one or more secondary diagnostic parameters at thesame time. Example, primary diagnostic parameters include intrathoracicimpedance and cardiovascular pressure. Example secondary diagnosticparameters include atrial fibrillation burden (AF), heart rate duringAF, ventricular fibrillation burden (VF), heart rate during VF, atrialtachyarrhythmia burden (AT), heart rate during AT, ventriculartachyarrhythmia burden (VT), heart rate during VT, activity level, heartrate variability, night heart rate, difference between day heart rateand night heart rate, heart rate turbulence, heart rate decelerationcapacity, respiratory rate, baroreflex sensitivity, percentage ofcardiac resynchronization therapy (CRT) pacing, metrics of renalfunction, weight, blood pressure, symptoms entered by the patient via aprogrammer, and patient history, such as medication history, or historyof heart failure hospitalizations. Thus, IMD 16 may, in variousembodiments, monitor either intrathoracic impedance or pressure and one,all, or any combination of the previously recited secondary diagnosticparameters.

IMD 16 detects worsening heart failure in patient 14 based on one orboth of the primary diagnostic parameters and the one or more secondarydiagnostic parameters. In particular, IMD 16 detects worsening heartfailure based only on the primary diagnostic parameter when an indexthat is changed over time based on the primary diagnostic parameter isoutside of a threshold zone. That is, when the index has a value that isgreater than the maximum threshold value of the threshold zone, theprimary diagnostic parameter may alone be a reliable indicator thatpatient 14 is experiencing worsening heart failure. When the index has avalue that is less than the minimum threshold value of the thresholdzone, the primary diagnostic parameter may alone be a reliable indicatorthat patient 14 is not experiencing worsening heart failure.

If the index is within the threshold zone, then IMD 16 detects worseningheart failure based on the secondary diagnostic parameter. In otherwords, the threshold zone may be thought of as a “maybe zone” withrespect to the primary diagnostic parameter. Accordingly, the secondarydiagnostic parameter may be used to provide additional evidence toconfirm that patient 14 is or is not experience worsening heart failure,when the index is within the threshold zone. In examples in which system10 monitors more than one secondary diagnostic parameter, system 10 maydetect worsening heart failure when the index is within the thresholdzone and one or more of the secondary diagnostic parameters satisfy thecorresponding conditions. The number of secondary diagnostic parametersrequired to must meet the corresponding conditions may be pre-determinedand/or selected by a user using programmer 24.

IMD 16 or programmer 24 may be configured to provide an alert inresponse to detecting worsening heart failure in patient 14. The alertmay be audible, visual, or tactile and enables patient 14 to seekmedical attention to treat the condition prior to experiencing a heartfailure event, or a clinician to direct patient 14 to do so. In someexamples, the alert may be a silent alert transmitted to another deviceassociated with a clinician or other user, such as a silent alerttransmitted to a server, as described below, and relayed to a physicianvia a computing device.

In some examples, system 10 may dynamically change the threshold zoneover time, i.e., change the values over which the index is conclusivefor detecting worsening heart failure. For example, system 10 mayautomatically increase or decrease the size of the threshold zone as afunction of time. The primary diagnostic parameter may become a morereliable indicator of worsening heart failure over time.

In another example, an authorized user may use programmer 24 to manuallychange the size of the threshold zone. In this way, an authorized usermay manually adjust the size of the threshold zone according to thehealth of patient 14. As an example, if symptoms of patient 14 areworsening, an authorized user may user programmer 24 to decrease thesize of the threshold zone.

In the example illustrated in FIG. 1, IMD 16 is configured to monitorintrathoracic impedance and includes leads 18, 20, and 22 extend intothe heart 12 of patient 14. Right ventricular (RV) lead 18 extendsthrough one or more veins (not shown), the superior vena cava (notshown), and right atrium 26, and into right ventricle 28. Leftventricular (LV) coronary sinus lead 20 extends through one or moreveins, the vena cava, right atrium 26, and into the coronary sinus 30 toa region adjacent to the free wall of left ventricle 32 of heart 12.Right atrial (RA) lead 22 extends through one or more veins and the venacava, and into the right atrium 26 of heart 12. Other configurations,i.e., number and position of leads, are possible. For example, otherleads or lead configurations may be used to monitor pressure and varioussecondary diagnostic parameters. As described above, in some examples,IMD 16 need not be coupled to leads.

Intrathoracic impedance, as well as various secondary diagnosticparameters, may be measured by creating an electrical path betweenelectrodes (not shown in FIG. 1) located on one or more of leads 18, 20,and 22 and can electrode 34. In some embodiments, the can of IMD 16 maybe used as an electrode in combination with electrodes located on leads18, 20, and 22. For example, system 10 may measure intrathoracicimpedance by creating an electrical path between RV lead 18 andelectrode 34. In additional embodiments, system 10 may include anadditional lead or lead segment having one or more electrodes positionedat a different location in the cardiovascular system or chest cavity,such as within one of the vena cava, subcutaneously at a locationsubstantially opposite IMD 16 vis-à-vis the thorax of patent 14, orepicardially, for measuring intrathoracic impedance.

In embodiments in which IMD 16 operates as a pacemaker, a cardioverter,and/or defibrillator, IMD 16 may sense electrical signals attendant tothe depolarization and repolarization of heart 12 via electrodes coupledto at least one of the leads 18, 20, 22. In some examples, IMD 16provides pacing pulses to heart 12 based on the electrical signalssensed within heart 12. The configurations of electrodes used by IMD 16for sensing and pacing may be unipolar or bipolar. IMD 16 may alsoprovide defibrillation therapy and/or cardioversion therapy viaelectrodes located on at least one of the leads 18, 20, 22. IMD 16 maydetect arrhythmia of heart 12, such as fibrillation of ventricles 28 and32, and deliver defibrillation therapy to heart 12 in the form ofelectrical pulses. In some examples, IMD 16 may be programmed to delivera progression of therapies, e.g., pulses with increasing energy levels,until a fibrillation of heart 12 is stopped. IMD 16 detects fibrillationemploying one or more fibrillation detection techniques known in theart.

It should be understood that IMD 16 may also include other types ofsensors for monitoring various other primary and secondary diagnosticparameters, or be coupled to additional medical leads carrying othertypes of sensors for monitoring other primary and secondary diagnosticparameters. In examples in which IMD 16 monitors pressure as the primarydiagnostic parameter, one or more of leads 18, 20, and 22 and/or thedevice can of IMD 16 may include one or more pressure sensors, such ascapacitive pressure sensors. IMD 16 may also include or be coupled toone or more pressure sensors, the output of which may be considered withheart rate to monitor baroreflex sensitivity as a secondary parameter.In another example, system 10 may include one or more accelerometers formonitoring activity of patient 14. In such examples, the accelerometersmay be contained within the device can of IMD 16. In some examples, IMD16 may include or be coupled to one or more sensors, e.g., chemicalsensors, pressure sensors, or electrodes for monitoring impedance, tomonitor metrics of renal function as one or more secondary diagnosticparameters. In some examples, IMD 16 may use electrodes on leads 18, 20,or 22, or other leads to detect respiration, e.g., based onintrathoracic impedance. In an additional example, IMD 16 may alsocommunicate with an external sensor, such as a scale for monitoring theweight of patient 14. Moreover, in embodiments in which IMD 16 isimplemented as an external device (not shown), leads for monitoringprimary and secondary diagnostic parameters may be implantedpercutaneously in patient 14 or attached to the skin of patient 14.

In some examples, programmer 24 may be a handheld computing device,computer workstation, or networked computing device. Programmer 24 mayinclude a user interface that receives input from a user. The userinterface may include, for example, a keypad and a display, which mayfor example, be a cathode ray tube (CRT) display, a liquid crystaldisplay (LCD) or light emitting diode (LED) display. The keypad may takethe form of an alphanumeric keypad or a reduced set of keys associatedwith particular functions. Programmer 24 can additionally oralternatively include a peripheral pointing device, such as a mouse, viawhich a user may interact with the user interface. In some embodiments,a display of programmer 24 may include a touch screen display, and auser may interact with programmer 24 via the display. It should be notedthat the user may also interact with programmer 24 remotely via anetworked computing device.

A user, such as a physician, technician, surgeon, electrophysiologist,or other clinician, may interact with programmer 24 to communicate withIMD 16. For example, the user may interact with programmer 24 toretrieve physiological or diagnostic information from IMD 16. A user mayalso interact with programmer 24 to program IMD 16, e.g., select valuesfor operational parameters of the IMD.

For example, the user may use programmer 24 to retrieve information fromIMD 16. The information may relate to the primary and/or secondarydiagnostic parameters, i.e., information relating to intrathoracicimpedance, pressure, AF burden, heart rate during AF, VF burden, heartrate during VF, AT burden, heart rate during AT, VT burden, heart rateduring VT, activity level, heart rate variability, night heart rate,difference between day heart rate and night heart rate, heart rateturbulence, heart rate deceleration capacity, respiratory rate,baroreflex sensitivity, percentage of CRT pacing, metrics of renalfunction, weight, blood pressure, symptoms entered by the patient via aprogrammer, and patient history, such as medication history, or historyof heart failure hospitalizations. The information may also includetrends therein over time. In some embodiments, the user may useprogrammer 24 to retrieve information from IMD 16 regarding other sensedphysiological parameters of patient 14. In addition, the user may useprogrammer 24 to retrieve information from IMD 16 regarding theperformance or integrity of IMD 16 or other components of system 10,such as leads 18, 20, and 22, or a power source of IMD 16.

The user may use programmer 24 to select a primary and one or moresecondary diagnostic parameters and program measurement parameters forthe selected diagnostic parameters. For example, the user may useprogrammer 24 to select intrathoracic impedance and/or cardiovascularpressure as the primary diagnostic parameter and to select one or moresecondary diagnostic parameters from a list of secondary diagnosticparameters. For example, if the user selects intrathoracic impedance asthe primary diagnostic parameter, the user may then use programmer 24 toselect electrodes and waveforms for measuring intrathoracic impedance.The user may select or specify measurement parameters for otherdiagnostic parameters in a similar manner.

In one example, a user may also use programmer 24 to program otherparameters related to detecting worsening heart failure, such asparameters associated with the threshold zone. In this case, the usermay specify parameters that define the threshold zone, i.e., the valuesover which the fluid index is inconclusive, or parameters that controlhow the threshold zone changes over time. Furthermore, the user may useprogrammer 24 to enter clinical information that can be used assecondary parameters, such as patient history, medication history,history of heart failure hospitalizations, or other historical orcurrent observations of patient condition.

Programmer 24 may also be used to program a therapy progression, selectelectrodes to deliver defibrillation pulses, select waveforms for thedefibrillation pulse, or select or configure a fibrillation detectionalgorithm for IMD 16. The user may also use programmer 24 to programaspects of other therapies provided by IMD 16, such as cardioversion orpacing therapies. In some examples, the user may activate certainfeatures of IMD 16 by entering a single command via programmer 24, suchas depression of a single key or combination of keys of a keypad or asingle point-and-select action with a pointing device.

IMD 16 and programmer 24 may communicate via wireless communicationusing any techniques known in the art. Examples of communicationtechniques may include, for example, low frequency or radiofrequency(RF) telemetry, but other techniques are also contemplated. In someexamples, programmer 24 may include a programming head that may beplaced proximate to the patient's body near the IMD 16 implant site inorder to improve the quality or security of communication between IMD 16and programmer 24.

FIG. 2 is a conceptual diagram illustrating IMD 16, leads 18, 20, and22, and electrode 34 of system 10 in greater detail. System 10 isgenerally described in this disclosure as a therapy system that detectsworsening heart failure in patient 14 and delivers corrective electricalsignals to heart 12. In particular, system 10 is as a therapy systemthat monitors intrathoracic impedance of tissue in the body of patient14 and one or more secondary diagnostic parameters to detect worseningheart failure in patient 14. It should be understood, however, thatsystem 10 may, in some embodiments, be implemented as a purelydiagnostic device that monitors a primary diagnostic parameter, such asintrathoracic impedance or cardiovascular pressure, and one or moresecondary diagnostic parameters.

In the example illustrated in FIG. 2, system 10 includes leads 18, 20,and 22 that include electrodes for monitoring intrathoracic impedanceand one or more secondary diagnostic parameters. Leads 18, 20, and 22may be electrically coupled to a stimulation generator and a sensingmodule of IMD 16 via connector block 38. In some examples, proximal endsof leads 18, 20, 22 may include electrical contacts that electricallycouple to respective electrical contacts within connector block 38. Inaddition, in some examples, leads 18, 20, 22 may be mechanically coupledto connector block 38 with the aid of set screws, connection pins, oranother suitable mechanical coupling mechanism.

Each of the leads 18, 20, 22 includes an elongated insulative lead body,which may carry a number of concentric coiled conductors separated fromone another by tubular insulative sheaths. In some cases, each of theleads 18, 20, 22 may include cable conductors. Bipolar electrodes 40 and42 are located adjacent to a distal end of lead 18. In addition, bipolarelectrodes 44 and 46 are located adjacent to a distal end of lead 20 andbipolar electrodes 48 and 50 are located adjacent to a distal end oflead 22.

Electrodes 40, 44 and 48 may take the form of ring electrodes, andelectrodes 42, 46 and 50 may take the form of extendable helix tipelectrodes mounted retractably within insulative electrode heads 52, 54and 56, respectively. In other embodiments, one or more of electrodes42, 46 and 50 may take the form of small circular electrodes at the tipof a tined lead or other fixation element. Leads 18, 20, 22 also includeelongated electrodes 62, 64, 66, respectively, which may take the formof a coil. Each of the electrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66may be electrically coupled to a respective one of the coiled conductorswithin the lead body of its associated lead 18, 20, 22, and therebycoupled to respective ones of the electrical contacts on the proximalend of leads 18, 20 and 22.

As discussed above, IMD 16 includes one or more housing electrodes, suchas housing electrode 34, which may be formed integrally with an outersurface of hermetically-sealed housing 60 of IMD 16 or otherwise coupledto housing 60. In some examples, housing electrode 34 is defined by anuninsulated portion of an outward facing portion of housing 60 of IMD16. Other division between insulated and uninsulated portions of housing60 may be employed to define two or more housing electrodes. In someexamples, housing electrode 34 comprises substantially all of housing60. As described in further detail with reference to FIG. 3, housing 60may enclose a signal generator that generates therapeutic stimulation,such as cardiac pacing pulses and defibrillation shocks, as well as asensing module for monitoring the rhythm of heart 12.

IMD 16 may sense electrical signals attendant to the depolarization andrepolarization of heart 12 via electrodes 34, 40, 42, 44, 46, 48, 50,62, 64 and 66. The electrical signals are conducted to IMD 16 from theelectrodes via the respective leads 18, 20, 22. IMD 16 may sense suchelectrical signals via any bipolar combination of electrodes 40, 42, 44,46, 48, 50, 62, 64 and 66. Furthermore, any of the electrodes 40, 42,44, 46, 48, 50, 62, 64 and 66 may be used for unipolar sensing incombination with housing electrode 34. Additionally, any of theelectrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66 may be used incombination with housing electrode 34 to sense intrathoracic impedanceof patient 14.

IMD 16 may process the sensed electrical signals to monitor secondarydiagnostic parameters such as AF burden, heart rate during AF, VFburden, heart rate during VF, AT burden, heart rate during AT, VTburden, heart rate during VT, activity level, heart rate variability,night heart rate, difference between day heart rate and night heartrate, heart rate turbulence, heart rate deceleration capacity, orbaroreflex sensitivity. IMD 16 may also process the intrathoracicimpedance sensed by electrodes 34, 40, 42, 44, 46, 48, 50, 62, 64, or 66as a primary diagnostic parameter to modify an index of worsening heartfailure, as well as to detect respiratory rate, depth, or pattern, whichmay be secondary diagnostic parameters.

In some examples, IMD 16 delivers pacing pulses via bipolar combinationsof electrodes 40, 42, 44, 46, 48 and 50 to produce depolarization ofcardiac tissue of heart 12. In some examples, IMD 16 delivers pacingpulses via any of electrodes 40, 42, 44, 46, 48 and 50 in combinationwith housing electrode 34 in a unipolar configuration. Furthermore, IMD16 may deliver cardioversion or defibrillation pulses to heart 12 viaany combination of elongated electrodes 62, 64, 66, and housingelectrode 34. Electrodes 34, 62, 64, 66 may also be used to delivercardioversion pulses, e.g., a responsive therapeutic shock, to heart 12.Electrodes 62, 64, 66 may be fabricated from any suitable electricallyconductive material, such as, but not limited to, platinum, platinumalloy or other materials known to be usable in implantabledefibrillation electrodes.

The configuration of therapy system 10 illustrated in FIGS. 1 and 2 ismerely one example. In other examples, a therapy system may includeepicardial leads and/or patch electrodes instead of or in addition tothe transvenous leads 18, 20, 22 illustrated in FIG. 1. Further, itshould be understood that system 10 may be configured to include othertypes of sensors for monitoring diagnostic parameters. As an example,system 10 may be configured to monitor cardiovascular pressure inpatient 14 as the primary diagnostic parameter and include one or morepressure sensors on leads 18, 20, and 22, or on an additional leadcoupled to IMD 16 and positioned within or proximate to thecardiovascular system of patient 14, e.g., within RV 28.

System 10 may be similarly configured to also include pressure sensorsto monitor the respiratory rate of patient 14. As an additional example,IMD 16 may, in some embodiments, include one or more accelerometers tomonitor the activity level of patient 14. The accelerometer may beenclosed in housing 60. In some examples, IMD 16 may include sensors tomonitor renal function. In some examples, system 10 may include one ormore external sensors to monitor a diagnostic parameter. For example,system 10 may include a scale for monitoring the weight of patient 14.In such an example, IMD 16 and the scale communicate with each other viatelemetry or a wired connection.

Moreover, IMD 16 need not be implanted within patient 14 as shown inFIG. 1. For example, IMD 16 may be implanted subcutaneously in patient14 or may be located outside the body of patient 14. In such examples,IMD 16 may monitor primary and secondary diagnostic parameters anddeliver defibrillation pulses and other therapies to heart 12 viapercutaneous leads that extend through the skin of patient 14 to avariety of positions within or outside of heart 12.

In addition, in other examples, system 10 may include any suitablenumber of leads coupled to IMD 16, and each of the leads may extend toany location within or proximate to heart 12 or in the chest of patient14. For example, other example therapy systems may include threetransvenous leads and an additional lead located within or proximate toleft atrium 36. As other examples, a therapy system may include a singlelead that extends from IMD 16 into right atrium 26 or right ventricle28, or two leads that extend into a respective one of the rightventricle 28 and right atrium 26.

FIG. 3 is a functional block diagram of one example of IMD 16, whichincludes a processor 80, memory 82, signal generator 84, electricalsensing module 86, telemetry module 88, power source 90, sensor 91 anddiagnostic unit 92. Processor 80 may comprise one or more processors.Memory 82 includes computer-readable instructions that, when executed byprocessor 80, cause IMD 16 and processor 80 to perform various functionsattributed to IMD 16 and processor 80 herein. Memory 82 may include anyvolatile, non-volatile, magnetic, optical, or electrical media, such asa random access memory (RAM), read-only memory (ROM), non-volatile RAM(NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory,or any other digital media.

Processor 80 may include any one or more of a microprocessor, acontroller, a digital signal processor (DSP), an application specificintegrated circuit (ASIC), a field-programmable gate array (FPGA), orequivalent discrete or integrated logic circuitry. In some examples,processor 80 may include multiple components, such as any combination ofone or more microprocessors, one or more controllers, one or more DSPs,one or more ASICs, or one or more FPGAs, as well as other discrete orintegrated logic circuitry. The functions attributed to processor 80herein may be embodied as software, firmware, hardware or anycombination thereof.

Processor 80 controls signal generator 84 to deliver stimulation therapyto heart 12 based on a selected one or more of therapy programs, whichmay be stored in memory 82. Specifically, processor 80 may controlsignal generator 84 to deliver electrical pulses with the amplitudes,pulse widths, frequency, or electrode polarities specified by theselected one or more therapy programs.

Signal generator 84 is electrically coupled to electrodes 34, 40, 42,44, 46, 48, 50, 62, 64, and 66, e.g., via conductors of the respectivelead 18, 20, 22, or, in the case of housing electrode 34, via anelectrical conductor disposed within housing 60 of IMD 16. A switchmatrix may also be provided to connect signal generator 84 to one ormore of electrodes 34, 40, 42, 44, 46, 48, 50, 62, 64, and 66. Signalgenerator 84 is configured to generate and deliver electricalstimulation therapy to heart 12.

For example, signal generator 84 may deliver defibrillation shocks toheart 12 via at least two of electrodes 34, 62, 64, 66. Signal generator84 may also deliver pacing pulses via ring electrodes 40, 44, 48 coupledto leads 18, 20, and 22, respectively, and/or helical electrodes 42, 46,and 50 of leads 18, 20, and 22, respectively. In some examples, signalgenerator 84 delivers pacing, cardioversion, or defibrillationstimulation in the form of electrical pulses. In other examples, signalgenerator 84 may deliver one or more of these types of stimulation inthe form of other signals, such as sine waves, square waves, or othersubstantially continuous time signals.

Signal generator 84 may include a switch module, and processor 80 mayuse the switch module to select, e.g., via a data/address bus, which ofthe available electrodes are used to deliver defibrillation pulses orpacing pulses. The switch module may include a switch array, switchmatrix, multiplexer, transistor array, microelectromechanical switches,or any other type of switching device suitable to selectively couplestimulation energy to selected electrodes.

Electrical sensing module 86 monitors signals from at least one ofelectrodes 34, 40, 42, 44, 46, 48, 50, 62, 64 or 66 in order to monitorelectrical activity of heart 12. Sensing module 86 may also include aswitch module to select which of the available electrodes are used tosense the heart activity. In some examples, processor 80 may select theelectrodes that function as sense electrodes via the switch modulewithin sensing module 86, e.g., by providing signals via a data/addressbus. In some examples, sensing module 86 includes one or more sensingchannels, each of which may comprise an amplifier. In response to thesignals from processor 80, the switch module within sensing module 86may couple the outputs from the selected electrodes to one of thesensing channels.

In some examples, one channel of sensing module 86 may include an R-waveamplifier that receives signals from electrodes 40 and 42, which areused for pacing and sensing in right ventricle 28 of heart 12. Anotherchannel may include another R-wave amplifier that receives signals fromelectrodes 44 and 46, which are used for pacing and sensing proximate toleft ventricle 32 of heart 12. In some examples, the R-wave amplifiersmay take the form of an automatic gain controlled amplifier thatprovides an adjustable sensing threshold as a function of the measuredR-wave amplitude of the heart rhythm.

In addition, in some examples, one channel of sensing module 86 mayinclude a P-wave amplifier that receives signals from electrodes 48 and50, which are used for pacing and sensing in right atrium 26 of heart12. In some examples, the P-wave amplifier may take the form of anautomatic gain controlled amplifier that provides an adjustable sensingthreshold as a function of the measured P-wave amplitude of the heartrhythm. Examples of R-wave and P-wave amplifiers are described in U.S.Pat. No. 5,117,824 to Keimel et al., which issued on Jun. 2, 1992 and isentitled, “APPARATUS FOR MONITORING ELECTRICAL PHYSIOLOGIC SIGNALS,” andis incorporated herein by reference in its entirety. Other amplifiersmay also be used. Furthermore, in some examples, one or more of thesensing channels of sensing module 84 may be selectively coupled tohousing electrode 34, or elongated electrodes 62, 64, or 66, with orinstead of one or more of electrodes 40, 42, 44, 46, 48 or 50, e.g., forunipolar sensing of R-waves or P-waves in any of chambers 26, 28, 36, or32 of heart 12.

In some examples, sensing module 84 includes a channel that comprises anamplifier with a relatively wider pass band than the R-wave or P-waveamplifiers. Signals from the selected sensing electrodes that areselected for coupling to this wide-band amplifier may be provided to amultiplexer, and thereafter converted to multi-bit digital signals by ananalog-to-digital converter for storage in memory 82 as an electrogram(EGM). In some examples, the storage of such EGMs in memory 82 may beunder the control of a direct memory access circuit. Processor 80 mayemploy digital signal analysis techniques to characterize the digitizedsignals stored in memory 82 to detect and classify the patient's heartrhythm from the electrical signals. Processor 80 may detect and classifythe patient's heart rhythm by employing any of the numerous signalprocessing methodologies known in the art.

If IMD 16 is configured to generate and deliver pacing pulses to heart12, processor 80 may include pacer timing and control module, which maybe embodied as hardware, firmware, software, or any combination thereof.The pacer timing and control module may comprise a dedicated hardwarecircuit, such as an ASIC, separate from other processor 80 components,such as a microprocessor, or a software module executed by a componentof processor 80, which may be a microprocessor or ASIC. The pacer timingand control module may include programmable counters which control thebasic time intervals associated with DDD, VVI, DVI, VDD, AAI, DDI, DDDR,VVIR, DVIR, VDDR, AAIR, DDIR and other modes of single and dual chamberpacing. In the aforementioned pacing modes, “D” may indicate dualchamber, “V” may indicate a ventricle, “I” may indicate inhibited pacing(e.g., no pacing), and “A” may indicate an atrium. The first letter inthe pacing mode may indicate the chamber that is paced, the secondletter may indicate the chamber that is sensed, and the third letter mayindicate the chamber in which the response to sensing is provided.

Intervals defined by the pacer timing and control module withinprocessor 80 may include atrial and ventricular pacing escape intervals,refractory periods during which sensed P-waves and R-waves areineffective to restart timing of the escape intervals, the pulse widthsof the pacing pulses, A-V intervals, and V-V intervals for cardiacresynchronization therapy (CRT). As another example, the pacer timingand control module may define a blanking period, and provide signalssensing module 86 to blank one or more channels, e.g., amplifiers, for aperiod during and after delivery of electrical stimulation to heart 12.As another example, the pacer timing and control module may controlintervals for delivery of refractory period stimulation or cardiacpotentiation therapy. The durations of these intervals may be determinedby processor 80 in response to stored data in memory 82. The pacertiming and control module of processor 80 may also determine theamplitude of the cardiac pacing pulses.

During pacing, escape interval counters within the pacer timing/controlmodule of processor 80 may be reset upon sensing of R-waves and P-waves.Stimulation generator 84 may include pacer output circuits that arecoupled, e.g., selectively by a switching module, to any combination ofelectrodes 34, 40, 42, 44, 46, 48, 50, 62, or 66 appropriate fordelivery of a bipolar or unipolar pacing pulse to one of the chambers ofheart 12. Processor 80 may reset the escape interval counters upon thegeneration of pacing pulses by stimulation generator 84, and therebycontrol the basic timing of cardiac pacing functions, includinganti-tachyarrhythmia pacing (ATP).

The value of the count present in the escape interval counters whenreset by sensed R-waves and P-waves may be used by processor 80 tomeasure the durations of R-R intervals, P-P intervals, PR intervals andR-P intervals, which are measurements that may be stored in memory 82.Processor 80 may use the count in the interval counters to detect anarrhythmia event, such as an atrial or ventricular fibrillation ortachycardia.

In some examples, processor 80 may operate as an interrupt drivendevice, and is responsive to interrupts from pacer timing and controlmodule, where the interrupts may correspond to the occurrences of sensedP-waves and R-waves and the generation of cardiac pacing pulses. Anynecessary mathematical calculations to be performed by processor 80 andany updating of the values or intervals controlled by the pacer timingand control module of processor 80 may take place following suchinterrupts. A portion of memory 82 may be configured as a plurality ofrecirculating buffers, capable of holding series of measured intervals,which may be analyzed by processor 80 in response to the occurrence of apace or sense interrupt to determine whether the patient's heart 12 ispresently exhibiting atrial or ventricular tachyarrhythmia.

In some examples, an arrhythmia detection method may include anysuitable tachyarrhythmia detection algorithms. In one example, processor80 may utilize all or a subset of the rule-based detection methodsdescribed in U.S. Pat. No. 5,545,186 to Olson et al., entitled,“PRIORITIZED RULE BASED METHOD AND APPARATUS FOR DIAGNOSIS AND TREATMENTOF ARRHYTHMIAS,” which issued on Aug. 13, 1996, or in U.S. Pat. No.5,755,736 to Gillberg et al., entitled, “PRIORITIZED RULE BASED METHODAND APPARATUS FOR DIAGNOSIS AND TREATMENT OF ARRHYTHMIAS,” which issuedon May 26, 1998. U.S. Pat. No. 5,545,186 to Olson et al. U.S. Pat. No.5,755,736 to Gillberg et al. are incorporated herein by reference intheir entireties. However, other arrhythmia detection methodologies mayalso be employed by processor 80 in other examples.

In the event that processor 80 detects an atrial or ventriculartachyarrhythmia based on signals from sensing module 86, and ananti-tachyarrhythmia pacing regimen is desired, timing intervals forcontrolling the generation of anti-tachyarrhythmia pacing therapies bysignal generator 84 may be loaded by processor 80 into the pacer timingand control module to control the operation of the escape intervalcounters therein and to define refractory periods during which detectionof R-waves and P-waves is ineffective to restart the escape intervalcounters.

If IMD 16 is configured to generate and deliver defibrillation pulses toheart 12, signal generator 84 may include a high voltage charge circuitand a high voltage output circuit. If IMD 16 is configured to generateand deliver pacing pulses to heart 12, signal generator 84 may include alow voltage charge circuit and a low voltage output circuit. In theevent that generation of a cardioversion or defibrillation pulse isrequired, processor 80 may employ the escape interval counter to controltiming of such cardioversion and defibrillation pulses, as well asassociated refractory periods. In response to the detection of atrial orventricular fibrillation or tachyarrhythmia requiring a cardioversionpulse, processor 80 may activate a cardioversion/defibrillation controlmodule, which may, like pacer timing and control module, be a hardwarecomponent of processor 80 and/or a firmware or software module executedby one or more hardware components of processor 80. Thecardioversion/defibrillation control module may initiate charging of thehigh voltage capacitors of the high voltage charge circuit of signalgenerator 84 under control of a high voltage charging control line.

Processor 80 may monitor the voltage on the high voltage capacitor maybe monitored, e.g., via a voltage charging and potential (VCAP) line. Inresponse to the voltage on the high voltage capacitor reaching apredetermined value set by processor 80, processor 80 may generate alogic signal that terminates charging. Thereafter, timing of thedelivery of the defibrillation or cardioversion pulse by signalgenerator 84 is controlled by the cardioversion/defibrillation controlmodule of processor 80. Following delivery of the fibrillation ortachycardia therapy, processor 80 may return signal generator 84 to acardiac pacing function and await the next successive interrupt due topacing or the occurrence of a sensed atrial or ventriculardepolarization.

Signal generator 84 may deliver cardioversion or defibrillation pulseswith the aid of an output circuit that determines whether a monophasicor biphasic pulse is delivered, whether housing electrode 34 serves ascathode or anode, and which electrodes are involved in delivery of thecardioversion or defibrillation pulses. Such functionality may beprovided by one or more switches or a switching module of signalgenerator 84.

Telemetry module 88 includes any suitable hardware, firmware, softwareor any combination thereof for communicating with another device, suchas programmer 24 (FIG. 1). Under the control of processor 80, telemetrymodule 88 may receive downlink telemetry from and send uplink telemetryto programmer 24 with the aid of an antenna, which may be internaland/or external. Processor 80 may provide the data to be uplinked toprogrammer 24 and the control signals for the telemetry circuit withintelemetry module 88, e.g., via an address/data bus. In some examples,telemetry module 88 may provide received data to processor 80 via amultiplexer.

In some examples, processor 80 may transmit atrial and ventricular heartsignals (e.g., electrocardiogram signals) produced by atrial andventricular sense amp circuits within sensing module 86 to programmer24. Programmer 24 may interrogate IMD 16 to receive the heart signals.Processor 80 may store heart signals within memory 82, and retrievestored heart signals from memory 82. Processor 80 may also generate andstore marker codes indicative of different cardiac events that sensingmodule 86 detects, and transmit the marker codes to programmer 24. Anexample pacemaker with marker-channel capability is described in U.S.Pat. No. 4,374,382 to Markowitz, entitled, “MARKER CHANNEL TELEMETRYSYSTEM FOR A MEDICAL DEVICE,” which issued on Feb. 15, 1983 and isincorporated herein by reference in its entirety.

As illustrated in FIG. 3, sensing module 86 may include an impedancemeasurement module 87. Processor 80 may control impedance measurementmodule 87 to periodically measure an electrical parameter to determinean impedance, such as a intrathoracic impedance. For a intrathoracicimpedance measurement, processor 80 may control stimulation generator 84to deliver an electrical signal between selected electrodes andimpedance measurement module 87 to measure a current or voltageamplitude of the signal. Processor 80 may select any combination ofelectrodes 34, 40, 42, 44, 46, 48, 50, 62, 64, and 66, e.g., by usingswitch modules in signal generator 84 and sensing module 86. Impedancemeasurement module 87 includes sample and hold circuitry or othersuitable circuitry for measuring resulting current and/or voltageamplitudes. Processor 80 determines an impedance value from theamplitude value(s) received from impedance measurement module 87.

In some examples, processor 80 may perform an impedance measurement bycausing signal generator 84 to deliver a voltage pulse between twoelectrodes and examining resulting current amplitude value measured byimpedance measurement module 87. In these examples, signal generator 84delivers signals that do not necessarily deliver stimulation therapy toheart 12, due to, for example, the amplitudes of such signals and/or thetiming of delivery of such signals. For example, these signals maycomprise sub-threshold amplitude signals that may not stimulate heart12. In some cases, these signals may be delivered during a refractoryperiod, in which case they also may not stimulate heart 12.

In other examples, processor 80 may perform an impedance measurement bycausing signal generator 84 to deliver a current pulse across twoselected electrodes. Impedance measurement module 87 holds a measuredvoltage amplitude value. Processor 80 determines an impedance valuebased upon the amplitude of the current pulse and the amplitude of theresulting voltage that is measured by impedance measurement module 87.IMD 16 may use defined or predetermined pulse amplitudes, widths,frequencies, or electrode polarities for the pulses delivered for thesevarious impedance measurements. In some examples, the amplitudes and/orwidths of the pulses may be sub-threshold, e.g., below a thresholdnecessary to capture or otherwise activate tissue, such as cardiactissue.

In certain cases, IMD 16 may measure intrathoracic impedance values thatinclude both a resistive and a reactive (i.e., phase) component. In suchcases, IMD 16 may measure impedance during delivery of a sinusoidal orother time varying signal by signal generator 84, for example. Thus, asused herein, the term “impedance” is used in a broad sense to indicateany collected, measured, and/or calculated value that may include one orboth of resistive and reactive components.

In the illustrated example shown in FIG. 3, IMD 16 includes diagnosticunit 92. Diagnostic unit 92 provides functionality that enables IMD 16to detect worsening heart failure in patient 14. To avoid confusion,although diagnostic unit 92 is described as performing the variousmonitoring and detecting techniques proscribed to IMD 16, it should beunderstood that these techniques may also be performed by processor 80,e.g., that diagnostic unit 92 may be a functional module provided orexecuted by processor 80. Accordingly, although processor 80 anddiagnostic unit 92 are illustrated as separate modules in FIG. 3,processor 80 and diagnostic unit 92 may be incorporated in a singleprocessing unit or equivalent circuitry.

In operation, diagnostic unit 92 monitors a primary diagnostic parameterand one or more secondary diagnostic parameters to detect worseningheart failure in patient 14. Diagnostic unit 92 may operate inaccordance with any detection algorithm described in this disclosure.The detection algorithm may be loaded from memory 82 or any othermemory. Example detection algorithms specify physiological parametersthat are used as the primary and second diagnostic parameters, thresholdzone characteristics, and detection rules. As an example, a detectionalgorithm may specify thransthoracic impedance for the primarydiagnostic parameter, AT/AF burden for the secondary diagnosticparameter, the range of index values for the threshold zone, and one ormore AT/AF burden conditions. If the detection algorithm provides formultiple secondary diagnostic parameters, such as AT/AF burden andactivity level, the detection algorithm specifies the rules used fordetecting worsening heart failure based on the AT/AF burden and activitylevel conditions, i.e., whether one or both of the AT/AF burden and theactivity level conditions must be satisfied in order to detect worseningheart failure in patient 14.

In the example illustrated in FIG. 3, diagnostic unit 92 may receivesignals or indications from processor 80, sensing module 86 or othersensors 91 to monitor the primary and secondary diagnostic parameters.Thus, IMD 16 may be configured to monitor physiological parameters thatare capable of being sensed using any combination of electrodes 34, 40,42, 44, 46, 48, 50, 62, 64 and 66. For example, IMD 16 may be configuredto monitor intrathoracic impedance and/or electrical activity of heart12, using any combination of electrodes 34, 40, 42, 44, 46, 48, 50, 62,64 and 66.

Based on the electrical activity of heart 12 as indicated by sensingmodule 86, diagnostic unit 92 may monitor AF burden, heart rate duringAF, VF burden, heart rate during VF, AT burden, heart rate during AT, VTburden, heart rate during VT, heart rate variability, night heart ratedifference between day heart rate and night heart rate, heart rateturbulence, heart rate deceleration capacity, or baroreflex sensitivity.As previously described, sensing module 86 monitors signals from aselected combination of electrodes 34, 40, 42, 44, 46, 48, 50, 62, 64,and 66 and processor 80/diagnostic unit 92 may detect atrial orventricular tachyarrhythmia based on signals or indications from sensingmodule 86. An AT burden may be determined based on the number and/orduration (individual, average, or collective) of incidents of AT, aswell as the ventricular rate during AT. AF, VT and VF burdens may besimilar determined. In some examples, AT and AF burdens are combined asan AT/AF burden. VT and VF burdens may likewise be combined, in someexamples. Such tachyarrhythmia burdens, as well as heart ratevariability and night heart rate, are examples of secondary diagnosticparameters that may be monitored by diagnostic unit 92.

IMD 16 may also be configured, in various examples, to monitor otherdiagnostic parameters. In some examples, IMD 16 may be configured toinclude other types of sensors, such as sensor 91 illustrated in FIG. 3,suitable for monitoring other primary and secondary diagnosticparameters, such as one or more pressure sensors for monitoring acardiovascular pressure in patient 14, one or more accelerometers formonitoring the activity level of patient 14, one or more pressuresensors for monitoring the heart rate variability and night heart rateof patient 14, and/or one or more pressure sensors for monitoring therespiratory rate, depth or pattern of patient 14. In such embodiments,pressure sensors may be carried by leads 18, 20, or 22 or by one or moreadditional leads coupled to IMD 16. In embodiments in which IMD 16monitors the activity level of patient 14, one or more accelerometersmay be contained within or positioned on the housing of IMD 16, may becarried by one or more of leads 18, 20, and 22 or one or more additionalleads, or may be a remote sensor in communication with IMD 16. Inaddition to fluid accumulation as a primary diagnostic parameter, insome examples, diagnostic unit 92 may monitor respiratory rate, depth orpattern of patient 14 as a secondary diagnostic parameter based on theintrathoracic impedance determined based on signals received fromimpedance measurement module 87. In some examples, IMD 16 may includesensors, such as chemical, pressure or fluid sensors, for monitoringrenal function. Furthermore, in some examples, diagnostic unit 92 mayreceive signals or information from external sources, such as programmer24 or an external sensor, such as a scale, and monitor such informationor signals as secondary diagnostic parameters. Additionally, diagnosticunit 92 may receive information from processor 80, or may maintaininformation in memory 82, indicating percentage of CRT pacing as asecondary diagnostic parameter. Diagnostic unit 92 or processor 80 maydetermine whether or not CRT pacing is delivered based on informationfrom processor 80 of a pacer timing and control module thereof.

If diagnostic unit 92 detects worsening heart failure of patient 14,diagnostic unit 92 may provide an alert to patient 14. Diagnostic unit92 may include or be coupled to an alert module (not shown) thatprovides, as examples, an audible or tactile alert to patient 14 of theworsening heart failure. In some examples, diagnostic unit 92additionally or alternatively provide an indication of worsening heartfailure to programmer 24 or another device via telemetry module 88and/or network, which may provide an alert to a user, such as patient 14or a clinician.

The various components of IMD 16 are coupled to power source 90, whichmay include a rechargeable or non-rechargeable battery. Anon-rechargeable battery may be capable of holding a charge for severalyears, while a rechargeable battery may be inductively charged from anexternal device, e.g., on a daily or weekly basis.

FIG. 4 is block diagram of an example programmer 24. As shown in FIG. 4,programmer 24 includes processor 100, memory 102, user interface 104,telemetry module 106, and power source 108. In some examples, programmer24, as illustrated in FIG. 4, includes a diagnostic unit 110. Programmer24 may be a dedicated hardware device with dedicated software forprogramming of IMD 16. Alternatively, programmer 24 may be anoff-the-shelf computing device running an application that enablesprogrammer 24 to program IMD 16.

A user may use programmer 24 to select worsening heart failure detectionalgorithms, e.g., select primary and secondary diagnostic parametersfrom a list of possible diagnostic parameters, select threshold zonecharacteristics, and select rules for detecting worsening heart failurein patient 14 based on the selected diagnostic parameters and thresholdzone. A user may also use programmer 24 to configure other sensing orany therapy provided by IMD 16. The clinician may interact withprogrammer 24 via user interface 104, which may include display topresent graphical user interface to a user, and a keypad or anothermechanism for receiving input from a user.

Processor 100 can take the form one or more microprocessors, DSPs,ASICs, FPGAs, programmable logic circuitry, or the like, and thefunctions attributed to processor 100 herein may be embodied ashardware, firmware, software or any combination thereof. Diagnostic unit110, although illustrated as a separate module in FIG. 4, may beincorporated in a single processing unit with processor 100 orfunctional module executed or provided by processor 100. Memory 102 maystore instructions that cause processor 100 and/or diagnostic unit 110to provide the functionality ascribed to programmer 24 herein, andinformation used by processor 100 and/or diagnostic unit 110 to providethe functionality ascribed to programmer 24 herein. Memory 102 mayinclude any fixed or removable magnetic, optical, or electrical media,such as RAM, ROM, CD-ROM, hard or floppy magnetic disks, EEPROM, or thelike. Memory 102 may also include a removable memory portion that may beused to provide memory updates or increases in memory capacities. Aremovable memory may also allow patient data to be easily transferred toanother computing device, or to be removed before programmer 24 is usedto program therapy for another patient. Memory 102 may also storeinformation that controls operation of IMD 16, such as therapy deliveryvalues.

A user, such as a clinician, technician, or patient 14, may interactwith programmer 24 via user interface 104. User interface 106 mayinclude display to present graphical user interface to a user, and akeypad or another mechanism for receiving input from a user. In someexamples, user interface 106 may include a touch screen display.

Programmer 24 may communicate wirelessly with IMD 16, such as using RFcommunication or proximal inductive interaction. This wirelesscommunication is possible through the use of telemetry module 106, whichmay be coupled to an internal antenna or an external antenna. Anexternal antenna that is coupled to programmer 24 may correspond to theprogramming head that may be placed over heart 12, as described abovewith reference to FIG. 1. Telemetry module 106 may be similar totelemetry module 88 of IMD 16 (FIG. 3).

Programmer 24 may also be configured to communicate with anothercomputing device via wireless communication techniques, or directcommunication through a wired, e.g., network, connection. Examples oflocal wireless communication techniques that may be employed tofacilitate communication between programmer 24 and another computingdevice include RF communication based on the 802.11 or Bluetoothspecification sets, infrared communication, e.g., based on the IrDAstandard.

Power source 108 delivers operating power to the components ofprogrammer 24. Power source 108 may include a battery and a powergeneration circuit to produce the operating power. In some embodiments,the battery may be rechargeable to allow extended operation. Rechargingmay be accomplished by electrically coupling power source 108 to acradle or plug that is connected to an alternating current (AC) outlet.In addition or alternatively, recharging may be accomplished throughproximal inductive interaction between an external charger and aninductive charging coil within programmer 24. In other embodiments,traditional batteries (e.g., nickel cadmium or lithium ion batteries)may be used. In addition, programmer 24 may be directly coupled to analternating current outlet to power programmer 24. Power source 108 mayinclude circuitry to monitor power remaining within a battery. In thismanner, user interface 104 may provide a current battery level indicatoror low battery level indicator when the battery needs to be replaced orrecharged. In some cases, power source 108 may be capable of estimatingthe remaining time of operation using the current battery.

In some examples, IMD 16 may detect worsening heart failure using any ofthe techniques described herein, and provide an indication of worseningheart failure to programmer 24. In such examples, programmer 24 need notinclude diagnostic module 110. Processor 100 may control user interface106 to provide an alert of worsening heart failure of patient 14 to thepatient, a clinician, or other users. In some examples, processor 100may provide an alert of worsening heart failure of patient 14 to one ormore computing devices via a network. A user may use programmer 24 toretrieve and/or view data regarding primary and secondary diagnosticparameters.

In some examples, programmer 24 includes diagnostic module 110 thatreceives diagnostic data from IMD 16, or other implanted or externalsensors or devices, i.e., data regarding the primary and secondarydiagnostic parameters, and processes the received data to detectworsening heart failure in patient 14. In this manner, diagnostic unit110 may perform substantially the same functionality as described withrespect to diagnostic unit 92 in FIG. 3. IMD 16 may not need to includediagnostic unit 92 in examples in which programmer 24 includesdiagnostic unit 110. Diagnostic unit 110 may include an alert modulethat provides an alert to patient 14 or a clinician via user interface104 when worsening heart failure is detected in patient 14, and/orprovides a notification to one or more computing devices via a network.

Alerts provided via user interface 104 may include a silent, audible,visual, or tactile alert. For example, user interface 104 may emit abeeping sound, display a text prompt, cause various buttons or screensto flash, or vibrate to alert patient 14 or another user that a heartfailure decompensation event may be likely to occur. Patient 14 may thenseek medical attention, e.g., check in to a hospital or clinic, toreceive appropriate treatment, or the other user may instruct patient 14to do so.

Although illustrated and described in the context of examples in whichprogrammer 24 is able to program the functionality of IMD 16, in otherexamples a device capable of communicating with IMD 16 and providingfunctionality attributed to programmer 24 herein need not be capable ofprogramming the functionality of the IMD. For example, an external homeor patient monitor may communicate with IMD 16 for any of the purposesdescribed herein, but need not independently be capable of programmingthe functionality of the IMD. Such as a device may be capable ofcommunicating with other computing devices via a network, as discussedin greater detail below.

The components of and functionality provided by a diagnostic unit fordetecting worsening heart failure are described in greater detail belowwith respect to diagnostic unit 92 of IMD 16. However, it is understoodthat any diagnostic unit provided in any device, such as diagnostic unit110 of programmer 24, may include the same or similar components andprovide the same or similar functionality.

FIG. 5 is a block diagram of an example configuration of diagnostic unit92. As shown in FIG. 5, diagnostic unit 92 includes multiple componentsincluding diagnostic module 120, impedance analysis unit 122, andsecondary parameter unit 124, and alert module 128. Because either IMD16 or programmer 24 may be configured to include a diagnostic unit,modules 120, 122, 124, and 128 (and their sub-modules described belowwith reference to FIGS. 6-8) may be implemented in one or moreprocessors, such as processor 80 of IMD 16 or processor 100 ofprogrammer 24. The modules of diagnostic unit 92 (and their sub-modulesdescribed below with reference to FIGS. 6-8) may be embodied as one ormore hardware modules, software modules, firmware modules, or anycombination thereof. As illustrated in FIG. 5, the modules andsub-modules of diagnostic unit 92 may have access to memory forbuffering or storing any of the values discussed with reference to FIGS.5-8, e.g., at locations accessible by and known to these modules.

Generally, diagnostic module 120 processes data received from impedanceanalysis unit 122 and secondary diagnostic parameter unit 124 to detectworsening heart failure in patient 14. Accordingly, impedance analysisunit 122 and secondary diagnostic parameter unit 124 may operate in acoordinated manner with diagnostic module 120. In one exampleembodiment, diagnostic module 120 may retrieve timing information frommemory 126. The timing information may provide periodic intervals formonitoring primary and secondary diagnostic parameters and detectingworsening heart failure based on the parameters. Accordingly, diagnosticmodule 120 may invoke impedance analysis unit 122 and secondaryparameter unit 124 based on the timing information. Alternatively,diagnostic module 120 may load the timing information into impedanceanalysis unit 122 and secondary parameter unit 124, and units 122 and124 may monitor corresponding parameters according to the timinginformation. In either case, diagnostic module 120, impedance analysisunit 122, and secondary parameter unit 124 operate together toperiodically monitor primary and secondary diagnostic parameters ofpatient 14 and detect worsening heart failure in patient 14 based on thediagnostic parameters.

Impedance analysis unit 122 monitors the intrathoracic impedance ofpatient 14 as previously described with respect to FIG. 3. That is,impedance analysis unit 122 may receive intrathoracic impedance valuesmeasured using the techniques described above with respect to FIG. 3.Although impedance analysis unit 122 is illustrated in FIG. 5, it shouldbe understood that impedance analysis unit 122 is one example of variousprimary diagnostic parameter analysis units that may be utilized. Inother example embodiments, diagnostic unit 92 may be configured toinclude, in place of impedance analysis unit 122, a pressure analysisunit that monitors one or more cardiovascular pressures of patient 14.

Secondary parameter unit 124 may monitor one or more secondarydiagnostic parameters and output corresponding data to diagnostic module120. For example, secondary diagnostic unit 124 may obtain measuredvalues, process the measured values to detect worsening heart failure,and output secondary parameter data that indicates whether worseningheart failure is detected in patient 14. With respect to FIG. 3,secondary diagnostic unit 124 may monitor secondary diagnosticparameters, e.g., AT/AF or VT burden, activity level, night heart,difference between day heart rate and night heart rate, heart rateturbulence, heart rate deceleration capacity, percentage of CRT pacing,heart rate variability, respiratory rate, and other parameters thatindicate worsening heart failure, based on signals or indicationsreceived from sensing module 86.

Diagnostic module 120 processes data received from impedance analysisunit 122 and secondary parameter unit 124 according to a detectiontechnique or algorithm. The detection technique may be loaded frommemory 82. Memory 82 may store a plurality of detection techniques. Eachdetection technique may specify primary and secondary diagnosticparameters, rules regarding determining a value of an index of worseningheart failure based on the primary diagnostic parameter, rules regardingthe threshold zone, and rules for detecting worsening heart failurebased on the index, threshold zone, and secondary diagnostic parameter.

The rules regarding the threshold zone may specify the range of valuesfor the threshold zone. If the threshold zone dynamically changes overtime, the rules may also control how the threshold zone changes as afunction of time or as a function of knowledge, such as knowledge of thecondition of patient 14. The rules for detecting worsening heart failuremay specify threshold values associated with the primary and secondarydiagnostic parameters. The threshold values correspond to a conditionthat must be satisfied to detect worsening heart failure. As an example,when multiple secondary diagnostic parameters are used one detectiontechnique may require that at least one secondary diagnostic parameterexceed a corresponding threshold value, and another detection techniquemay require that each of the secondary diagnostic parameters exceed acorresponding threshold value.

Diagnostic module 120 invokes alert module 128 in response to detectingworsening heart failure in patient 14. Alert module 128 provides analert to patient 14 by, for example, providing an audible, visual, ortactile alert. Alert module 128 may cause IMD 16 to emit a beeping asound or vibrate. In some examples, alert module 128 may provide analert by communicating with an external device, such as programmer 24.In response to the communication from alert module 128, programmer 24may emit a beeping sound, display a text prompt, vibrate, or causebuttons and/or screens of programmer 24 to flash. Similarly, if thealert module is implemented in programmer 24, alert module 128 may causeprogrammer 24 to send a telemetry signal to IMD 16 that causes IMD 16 togenerate the alert.

FIG. 6 is a block diagram of an example configuration of impedanceanalysis unit 122. As shown in FIG. 6, impedance analysis unit 122includes a current impedance module 130, a reference impedance module132 and a fluid index module 134. In general, impedance analysis unit122 periodically receives (or accesses) intrathoracic impedance valuesmeasured as described above, and determines, e.g., updates, a value of afluid index 138 based on the impedance values. Impedance analysis unit122 provides the current fluid index value 140 to diagnostic module 120(FIG. 5) for comparison to the threshold zone.

The fluid index may reflect a level of fluid accumulation, e.g.,pulmonary edema. The fluid index is one example of an index thatindicates worsening heart failure. Other examples include indices ormetrics of increased ventricular filling pressures or other morbiditiesassociated with worsening heart failure experienced by a patient. Ingeneral, any parameter described herein as indicating worsening heartfailure may be a primary diagnostic parameter, and an index thatindicates worsening heart failure may be any index that is incrementedto indicate a trend in the primary diagnostic parameter (that reflectsworsening heart failure).

Impedance measurement module 87 and/or processor 80 (FIG. 3) may measureimpedance values on an hourly basis, daily basis, weekly basis, or otherperiodic interval. In one example embodiment, impedance measurementmodule 87 may measure impedance values during a particular portion of aday. As an example, impedance measurement module 87 may measureimpedance values every twenty minutes during the afternoon. In someexamples, current impedance module 130 determines a current impedancevalue 136 as an average or median of a plurality of such measuredvalues, e.g., a daily average. Current impedance module 130 may utilizea buffer to store a plurality of measured impedance values to determinecurrent impedance value 136. In other examples, current impedance value136 may be a single, most recently measured impedance value.

Reference impedance module 132 generates a reference impedance value 138based on the current impedance values 136 determined by currentimpedance module 130 over time. For example, reference impedance module132 may compare current impedance value 136 to a previous currentimpedance value, and determine a new reference impedance value 138 basedon the comparison. Reference impedance module 132 may generate a newreference impedance value 138 based on the prior reference impedancevalue.

For example, when the current impedance value 136 is greater than theprevious impedance value, reference impedance module 132 may generate anew reference impedance value 138 by adding a predetermined value to theprevious reference impedance value. Similarly, reference impedancemodule 132 may generate a new reference impedance value 138 bysubtracting a predetermined value from the prior reference impedancevalue if the current impedance value is less than a previous impedancevalue. In other words, reference impedance module 132 may generatereference impedance values 138 by incrementing or decrementing thereference impedance value based on the comparison of the currentimpedance value 136 to the previous impedance value. In other examples,reference impedance module 132 may determine reference impedance valueas an average or median, e.g., over a window, of previous impedancevalues 136. Reference impedance module 132 may utilize buffers or othermemory to store previous impedance values 136.

Fluid index value 140 represents decreasing intrathoracic impedance inpatient 14, and is accumulated over time to detect worsening heartfailure. Fluid index module 134 determines, e.g., changes, fluid indexvalue 140 based on a comparison of current impedance value 136 toreference impedance value 138. For example, fluid index module 134 mayincrement fluid index value 134 by the difference between currentimpedance value 136 and reference impedance value 138 when the currentimpedance value is less than the reference impedance value for aparticular measurement interval. Fluid index module 134 may decrementfluid index value 140 when the current impedance value is greater thanthe reference impedance value for a particular measurement interval. Thedecrement may be by the difference between current impedance value 136and reference impedance value 138, by or to a predetermined value, or toa value of zero. In some examples, impedance analysis unit may determinecurrent impedance value 136, reference impedance value 138 and fluidindex value 140 using any of the techniques described in acommonly-assigned and co-pending U.S. application by Sarkar et al.,entitled “DETECTING WORSENING HEART FAILURE BASED ON IMPEDANCEMEASUREMENTS,” filed on even date herewith, and/or commonly-assignedU.S. application Ser. No. 10/727,008 by Stadler et al., entitled “METHODAND APPARATUS FOR DETECTING CHANGE IN INTRATHORACIC IMPEDANCE,” filed onDec. 3, 2003. Each of these preceding applications by Sarkar et al. andStadler et al. are incorporated herein by reference in their entirety.As mentioned above, impedance analysis unit 122 provides the fluid indexvalue 140 to diagnostic module 120 (FIG. 5) for comparison to thethreshold zone in the described in greater detail below. Diagnosticmodule 120 compares fluid index value 140 to the threshold zone todetermine whether to provide an alert to patient 14, continue monitoringpatient 14, or examine the secondary diagnostic parameter.

FIG. 7 is a block diagram illustrating the functionality of secondaryparameter unit 124. In general, secondary parameter unit 124 receivesphysiological parameter or therapy data 150, and determines secondaryparameter values 152 based on the physiological parameter or therapydata. Secondary parameter values 152 may be used by diagnostic module120 (FIG. 5) to detect worsening heart failure in patient 14.

Although secondary parameter unit 124 is described generally withrespect to FIG. 7, i.e., described without reference to a specificsecondary diagnostic parameter, it should be understood that secondaryparameter unit 124 may be used to determine secondary parameter values152 for any of the secondary diagnostic parameters discussed above.Furthermore, second parameter unit 124 may determine secondary parametervalues 152 for a plurality of secondary diagnostic parameters or,alternatively, diagnostic unit 92 may include a secondary parameter unit124 for each secondary diagnostic parameter used to detect worseningheart failure in patient 14.

For example, secondary parameter unit 124 or multiple secondaryparameter units may generate secondary parameter values 152 for AFburden, AT burden, AT/AF burden, VT burden, patient activity, nightheart rate, difference between day heart rate and night heart rate,heart rate turbulence, heart rate deceleration capacity, baroreflexsensitivity, percentage of CRT pacing, heart rate variability,respiration rate, respiration depth, respiration pattern, renalfunction, patient weight, or patient history. Secondary parameter unit124 may receive physiological parameter data 150 from one or more ofelectrical sensing module 86, implanted or external sensors 91,processor 80, or programmer 24 to determine the secondary parametervalues 152, e.g., to process data 150 such that is in a form that may beindicative of worsening heart failure. Physiological parameter data 150may include, as examples, heart rate, indications of the number andduration of AF, AT, or VT episodes, as well as the ventricular rateduring such episodes, or digitized intrathoracic impedance signals fordetermining respiration rate, depth or pattern. In some examples,secondary parameter values 152 may include variable values, such ascount variables that are updated, i.e., incremented or decremented orset to a predetermined value, based on received physiological parameterdata 150.

FIG. 8 is a block diagram of an example configuration of diagnosticmodule 120. As shown in FIG. 8, diagnostic module 120 includescomparison module 160, threshold zone module 162, time update module164, knowledge update module 166, threshold zone values 168, andsecondary parameter threshold values 169. Generally, comparison module160 detects worsening heart failure in patient 14 by comparing primarydiagnostic parameter values, e.g., fluid index values 140 received fromimpedance analysis unit 122 (FIG. 6), to values retrieved from thresholdzone module 162, and secondary parameter values 152 received fromsecondary parameter unit 124 (FIG. 7) to secondary parameter thresholdvalues 169. Comparison module 160 activates alert module 128 (FIG. 5) inresponse to detecting worsening heart failure.

Threshold zone module 162 stores values in threshold zone values 168that may be variable values and may be output to comparison module 160.The variable values in threshold zone values 168 define the thresholdzone and may include threshold values, THRESHOLD_HIGH and THRESHOLD_LOW.In other words, THRESHOLD_HIGH and THRESHOLD_LOW define a range ofvalues that is the threshold zone.

Time update module 164 and knowledge update module 166 may update thethreshold values in threshold zone values 168. As an example, timeupdate module 164 may automatically update the threshold values as afunction of time to, for example, increase or decrease the size of thethreshold zone as time lapses. Time update module 164 may alsoautomatically update the threshold values such that the threshold zoneis defined differently over predetermined intervals of time. As anotherexample, knowledge update module 166 may update the threshold values inthreshold zone values 168 based on input received from an authorizeduser of programmer 24. In this way, the size and range of the thresholdzone may be manually controlled and adapted based on the symptoms ofpatient 14. Furthermore, in some examples, knowledge update module 166may automatically update the threshold values of threshold zones values168 based on, for example, changes in patient condition observed via oneor more of the monitored diagnostic parameters, or indications ofefficacy of the diagnostic module 120 in identifying worsening heartfailure.

Initially, comparison module 160 compares fluid index value 140, whichis determined based on the primary diagnostic parameter, e.g.,intrathoracic impedance, as described above to threshold zone values168. When the fluid index value is outside the range of the thresholdzone values 168, i.e. greater than THRESHOLD_HIGH and less thanTHRESHOLD_LOW, the primary diagnostic parameter value is conclusive.That is, if the fluid index value is greater than THRESHOLD_HIGH, thencomparison module 160 activates alert module 128. If, on the other hand,fluid index value 140 is less than THRESHOLD_LOW, IMD 16 continues tomonitor patient 14.

However, when fluid index value 140 is within the range of the thresholdzone values 138, the primary diagnostic parameter is considered“inconclusive” and comparison module 160 compares one or more secondarydiagnostic parameter values 152 to the corresponding secondary parameterthreshold values 169. Comparison module 160 detects worsening heartfailure in patient 14 based on these comparisons. More specifically,comparison module 160 detects worsening heart failure based on thecomparisons in accordance with the particular detection technique.

As previously described, a detection technique specifies the secondarydiagnostic parameters, threshold values for comparison to the parametervalues, and a condition. Comparison module 160 detects worsening heartfailure and invokes alert module 128 (FIG. 5) when the condition issatisfied. As an example, the condition may be satisfied when asecondary diagnostic parameter value 152 exceeds the correspondingsecondary diagnostic parameter threshold value 169. However, in anexample using multiple secondary diagnostic parameters, differentdetection techniques specify different conditions, such as a conditionthat all parameter values exceed corresponding threshold values or, acondition that at least one parameter value exceeds the correspondingthreshold value.

FIG. 9 is a flow diagram illustrating an example method for detectingworsening heart failure in patient 14. The method may be performedentirely by IMD 16 or by a combination of IMD 16 and programmer 24. Whenthe method is performed by IMD 16 and programmer 24, the steps formonitoring primary and secondary diagnostic parameters, i.e., measuringthe primary and secondary diagnostic parameters, may be performed by IMD16 and the steps for detecting worsening heart failure in patient 14based on the primary and secondary diagnostic parameters may beperformed by programmer 24. In such examples, IMD 16 transmits parameterinformation to programmer 24 via wireless signals as previouslydescribed in this disclosure. For purposes of illustration only, it willbe assumed in the subsequent description that IMD 16 performs the methodillustrated in FIG. 9. Additionally, the method will be described withrespect to diagnostic unit 92 (FIG. 5) and diagnostic module 120 (FIG.6), but may be performed by any diagnostic unit(s) in any one or moredevices.

In the example shown in FIG. 9, IMD 16 monitors primary and secondarydiagnostic parameters (180). Based on the primary diagnostic parameter,IMD 16 determines a fluid index value 140 (181). In one example, IMD 16may periodically measure intrathoracic impedance, and an impedanceanalysis unit 122 may determine the fluid index value in the mannerdescribed above.

Diagnostic module 120 receives the fluid index value 140 value fromimpedance analysis unit 122 and compares it to a higher threshold value,THRESH_HIGH (182). In particular, comparison module 160 compares thefluid index value 140 to the high threshold value stored in thresholdzone values 168. If the fluid index value is greater than the highthreshold value (“YES” branch of step 182), then alert module 128 ofdiagnostic unit 92 generates an alert (190) that indicates worseningheart failure to patient 14. If, however, the fluid index value 140 isless than the high threshold value (“NO” branch of step 182), thendiagnostic module 120 compares the fluid index value to a lowerthreshold value, THRESH_LOW (184). In particular, comparison module 160may compare fluid index value 140 to the low threshold value stored inthreshold zone values 168.

When fluid index value 140 is less than the low threshold value, thenIMD 16 may update the threshold zone (192). As previously described, thethreshold zone may be updated, i.e., the size and range of the thresholdzone may change, as a function of time or based on knowledge of thecondition of patient 14. Time update module 164 and knowledge updatemodule 166 of threshold zone module 162 (FIG. 8) may update thethreshold zone by updating the higher and lower threshold values storedin threshold zone values 168. Threshold zone module 162 may updatethreshold zone values 168 periodically, and such updating need not occurafter each comparison of fluid index value 140 to the threshold zonevalues. In some embodiments, the threshold zone is constant and notupdated. Whether or not the threshold zone is updated, IMD 16 maycontinue to monitor the primary and secondary diagnostic parameters(180).

When fluid index value 140 is within the threshold zone, e.g., greaterthan the lower threshold value and less than the higher threshold value,or between the threshold values (“NO” branch of step 184), diagnosticmodule 120 determines whether the secondary diagnostic parameter(s).That is, diagnostic module 120 looks to the secondary diagnosticparameters for determining whether the patient is experiencing worseningheart failure when fluid index value 140 is within the threshold zone.

As discussed above, secondary parameter unit 124 may monitor one or moresecondary diagnostic parameters to determine secondary diagnosticparameter values, and comparison module 160 of diagnostic module 120 maycompare the values to corresponding threshold values to detect worseningheart failure in patient 14. As will be described in greater detail inFIGS. 11-14, comparison module 160 generates secondary parameter data,SECONDARY_DATA, based on the comparison. The secondary parameter datamay be a Boolean variable that is set to a true value to indicateworsening heart failure, or a false value if the secondary diagnosticparameter does not indicate worsening heart failure.

Diagnostic module 120 examines the secondary diagnostic parameter datato detect worsening heart failure in patient 14 (186). When thesecondary parameter data value is equal to a true value (“YES” branch ofstep 188), the secondary diagnostic parameter corroborates the primarydiagnostic parameter and alert module 128 generates an alert (190) toindicate worsening heart failure to patient 14. On the other hand, whenthe secondary parameter value is not equal to a true value (“NO” branchof step 188), i.e., equal to a false value, IMD 16 may update thethreshold zone (192) and/or continue to monitor the primary andsecondary diagnostic parameters (180).

The method shown in FIG. 9 may be performed periodically. That is, themethod may be repeated recursively over periodic intervals. For example,the method may repeat once per day, once every hour, once every severalhours, once an hour for a sub-period of several hours every day, and thelike.

FIG. 10 is a flow diagram illustrating an example method for measuringintrathoracic impedance and determining a fluid index value 140 inpatient 14. In particular, the method illustrated in FIG. 10 isdescribed with respect to impedance analysis unit 122 and fluid indexmodule 134 of FIG. 6. Initially, impedance analysis unit 122 determinesa current impedance value, CURRENT_Z, based on one or more measuredimpedance values received from impedance measurement module 87 and/orprocessor 80 (200). The measured impedance values may be collected atregular intervals throughout the day or during a particular portion ofthe day. In one example embodiment, impedance analysis unit 122 maydetermine the current impedance value as the average of impedance valuesmeasured every 20 minutes from the hours of 12 p.m. to 5 p.m. during oneday. Impedance analysis unit 122 then determines a short term meanimpedance value (MEAN_Z) (201). The short term mean may be the mean orweighted mean of the CURRENT_Zs from a plurality of days, e.g., the lastthree days. To determine the current and mean impedances, impedanceanalysis unit 122 may employ the techniques described in U.S.application Ser. No. 10/727,008 by Stadler et al., entitled “METHOD ANDAPPARATUS FOR DETECTING CHANGE IN INTRATHORACIC IMPEDANCE,” filed onDec. 3, 2003, and incorporated herein by reference in its entirety.

Fluid index module 134 compares the mean impedance value to a referenceimpedance value (202). When the mean impedance value is less than thereference impedance value (“YES” branch of step 202), fluid index module134 increases fluid index value 140 (204). As previously described,fluid index module 134 may increase the fluid index value by adding thedifference between the current impedance value and the referenceimpedance value to the previous fluid index value. In this way, thefluid index value accumulates over time while the mean impedance valueis less than the reference impedance value. However, when the meanimpedance value is greater than or equal to the reference impedancevalue (“NO” branch of step 202), fluid index module 134 resets the fluidindex value 140, e.g., to zero (206). In some examples, fluid indexmodule 134 may alternatively decrease fluid index 140 by the differencebetween the current and reference impedances, by a fixed orpredetermined amount, or to a fixed or predetermined value.

In either case, reference impedance module 132 also determines thereference impedance value 138 (REF_Z) for the next iteration of themethod based on the mean impedance value (208). For example, referenceimpedance module 132 may increment reference impedance value 138 by afixed amount if the mean impedance value 136 is greater than thereference impedance value 138. Reference impedance module 132 maydecrement reference impedance value 138 by the same or a different fixedamount if the mean impedance value 136 is less than the referenceimpedance value 138. In other examples, reference impedance module 132may update a running average or median (e.g., over a window) based onthe current impedance value 136.

FIGS. 11-15 are flow diagrams illustrating example methods formonitoring secondary diagnostic parameters to determine whether apatient is experiencing worsening heart failure. In particular, the flowdiagrams illustrated in FIGS. 11-15 are described with respect tosecondary parameter unit 124 shown in FIG. 7 and diagnostic unit 120 ofFIG. 8.

FIG. 11 is a flow diagram illustrating an example method for determiningwhether a patient is experiencing worsening heart failure based onatrial tachycardia and atrial fibrillation in patient 14. Initially,secondary parameter unit 124 measures an AF burden of patient 14 (210).For example, secondary parameter unit 124 may determine an AF burdenvalue based on the number and/or duration, e.g., average or cumulativeduration, of AF episodes experienced by patient 14, as well as theventricular rate, e.g. average ventricular rate during the episodes.

Next, comparison module 160 compares the measured AF burden value(AFburden) to a corresponding minimum threshold value 212 (minAFburden).If the AF burden value is greater than the minimum threshold value(“YES” branch of step 212), comparison module 160 sets the value of acount variable, ATAFevidenceCounter equal to a predetermined value,AFwin (214). If, however, the AF burden value is less than or equal tothe minimum threshold value (“NO” branch of step 212), comparison module160 decrements the count variable (216). The value of the count variableis generally not decremented lower than zero.

Secondary parameter unit 124 may also measure an AT/AF burden of patient14 (218). For example, secondary parameter unit 124 may determine anAT/AF burden value based on the AF burden value and an AT burden value,e.g., the sum of these values. The AT burden value may be determinedbased on the number and/or duration, e.g., average or cumulativeduration, of AT episodes experienced by patient 14, as well as theventricular rate, e.g. average ventricular rate during the episodes.

Comparison module 160 compares the AT/AF burden value (ATAFburden) to acorresponding maximum threshold value (maxAFburden) (220). When theAT/AF value is greater than the maximum threshold value (“YES” branch ofstep 220), comparison module 160 increments a count variable,chronicATAFcounter (224). However, when the AT/AF value is not greaterthan the maximum threshold value (“NO” branch of step 220), comparisonmodule 160 resets the count variable (226). In some examples, comparisonmodule 160 may additionally consider the ventricular rate during AT/AF,e.g., determine whether the AT/AF burden was greater than a thresholdnumber of hours and the ventricular rate during the AT/AF was greaterthan a threshold rate, to determine whether to increment the chronicAT/AF counter. In other examples, only AT/AF associated with a thresholdventricular rate may be counted as AT/AF burden that is compared to themaxAFburden threshold. In these ways, the devices according to thisdisclosure may consider whether AT/AF was conducted to the ventricles.

Diagnostic module 120 compares the count variable, chronicATAFcounter,to a threshold value, chronicAFduration, and the count variable,ATAFevidenceCounter, to a threshold value, zero (228). In this way, thiscomparison is used to determine whether the AT/AF burden satisfiescorresponding conditions that corroborate worsening heart failure inpatient 14. In some examples, when both conditions are satisfied (“YES”branch of step 228), comparison module 160 sets a Boolean variable(ATAF_DATA) equal to true (230). However, when either condition is notsatisfied in such examples (“NO” branch of step 228), the comparisonmodule 160 sets the AT/AF variable equal to false (232).

Diagnostic module 120 uses the secondary parameter data, e.g., theBoolean variable to determine whether the secondary diagnosticparameters satisfy the predetermined condition (186 of FIG. 9), e.g.,when the variable is true, to detect worsening heart failure in patient14. In some examples, diagnostic module 120 does not maintain a Booleanvariable (ATAF_DATA), but instead determines whether both conditions aresatisfied in response to determining that the fluid index is within thethreshold zone (182 and 184 of FIG. 9). The various values and countersdiscussed with respect to FIG. 11 may be modified on periodic basis,e.g., hourly or daily, and the example method of FIG. 11 may also beperformed on a periodic basis. The various values, e.g., AT/AF burdenvalues, may be daily values, weekly values, or the like, and may beaverage or median values.

FIG. 12 is a flow diagram illustrating an example method for determiningwhether a patient is experiencing worsening heart failure based onventricular tachycardia and ventricular fibrillation in patient 14. Themethod illustrated in FIG. 12 begins with secondary parameter unit 124determining a VT/VF burden value (240). In particular in this example,secondary parameter unit 124 determines a number of VT and/or VFepisodes. The number of VT/VF episodes may be a daily (or weekly ormonthly) total, or an average or median of a number of such totals,e.g., of the totals for the previous N days. In other examples, a VT/VFburden value may be determined based on the duration of the episodes, orthe ventricular rate during such episodes, as examples.

Comparison module 160 may compare the number of episodes (VTVFepi) to athreshold value (minVTepi) (242). When the number of measured VT/VFepisodes is greater than the threshold value (“YES” branch of step 242),comparison module 160 sets the value of a count variable(VTVFevidenceCounter) equal to a predetermined value (VTwin) (244). Onthe other hand, each day (or other period) when the number of measuredVT/VF episodes is not greater than the threshold value (“NO” branch ofstep 242), comparison module 160 decrements the count variable (246).

In some examples, comparison module 160 may additionally consider theventricular rate during VT/VF, e.g., determine whether the VT/VF burdenwas greater than a threshold number of hours and the ventricular rateduring the VT/VF was greater than a threshold rate, to determine whetherto set or decrement the VT/VF counter. In other examples, only VT/VFassociated with a threshold ventricular rate may be counted as VT/VFburden for setting or decrementing the counter.

To determine whether the VT/VF condition corroborates the primarydiagnostic parameter evidence indicating worsening heart failure inpatient 14, comparison module 160 compares the count variable to acorresponding threshold value (248). In the illustrated example thethreshold value is equal to zero. Accordingly, if the count variable isgreater than zero (“YES” branch of step 248), then comparison module 160sets the secondary parameter data, e.g., Boolean variable VTVF_DATAequal to true (250). However if the count variable is not greater thanzero (“NO” branch of step 248), comparison module 160 sets the secondaryparameter data value equal to false (252).

Diagnostic module 120 uses the secondary parameter data, e.g., theBoolean variable, to determine whether the secondary diagnosticparameters satisfy the predetermined condition (186 of FIG. 9 to detectworsening heart failure in patient 14. In some examples, diagnosticmodule 120 does not maintain a Boolean variable (VTVF_DATA), but insteaddetermines whether VTVFevidenceCounter is greater than the threshold,e.g., zero, in response to determining that the fluid index is withinthe threshold zone (182 and 184 of FIG. 9).

FIG. 13 is a flow diagram illustrating an example method for determiningwhether a patient is experiencing worsening heart failure based on theactivity level of patient 14. Initially, secondary parameter unit 124receives a signal, e.g., from a sensor 91, or data that indicates anactivity level of patient 14 (260). In some embodiments, the activitylevel of patient 14 may be measured at periodic intervals throughout theday or over a portion of the day. Multiple measurements may be averagedto obtain a daily value, or a value associated with some other periodgreater than the measurement frequency. Next, secondary parameter unit124 may determine a median activity level (MEDIAN_ACTIVITY) of patient14 (262). The median value may be determined as the median of the last“X” number of daily (or some other period) average activity levelvalues.

Comparison module 160 determines the ratio of the median activity levelto a baseline activity level, and compares the ratio to a firstthreshold value (activityFRACTION) and the median activity level toanother threhsold value (minACTIVITY) (264). The baseline activity levelmay be defined as the median activity level prior to the fluid indexentering the threshold zone. The activityFRACTION threshold value may becomputed as a predetermined or variable fraction of the previous medianactivity level, i.e., the median activity level prior to inclusion ofthe current daily value.

In this manner, a secondary diagnostic parameter, in this case activitylevel, may be compared to both an absolute threshold, in this caseminAcCTIVITY, which indicates whether the parameter has reached a levelat which it is considered indicative of worsening heart failure, and athreshold that indicates a rate of change, in this caseactivityFRACTION, which indicates whether the parameter has changed at arate that considered indicative of worsening heart failure. Othersecondary parameters, such as heart rate variability and night heartrate, which are discussed below, may be similarly compared to multiplethresholds, which may be absolute and related to a rate of change.

When the current median activity level is less than either of thesethreshold values, the activity level condition is satisfied (“YES”branch of step 264), and comparison module 160 sets the secondaryparameter data equal to true (266). However, when both conditions arenot satisfied (“NO” branch of step 264), comparison module 160 sets thesecondary parameter data value equal to false (268). In some examples,the analysis of activity level may include use of an activity levelindex similar to the fluid index, which may accumulate over time as themedian activity or ratio of median to baseline activity is less than anadaptive threshold, such as activity fraction. The index may be comparedto a threshold to determine whether to set the secondary parameter datavalue to a true or false value. Secondary parameter unit 124 outputs thesecondary parameter data to diagnostic module 120 in diagnostic unit 92for use in step 188 (FIG. 9) to detect worsening heart failure inpatient 14.

Diagnostic module 120 uses the secondary parameter data, e.g., theBoolean variable, to determine whether the secondary diagnosticparameters satisfy the predetermined condition (186 of FIG. 9 to detectworsening heart failure in patient 14. In some examples, diagnosticmodule 120 does not maintain a Boolean variable, but instead determineswhether the median activity level is less than one or more thresholds inresponse to determining that the fluid index is within the thresholdzone (182 and 184 of FIG. 9).

FIG. 14 is a flow diagram illustrating an example method for determiningwhether a patient is experiencing worsening heart failure based on theheart rate variability (HRV) of patient 14. Initially, secondaryparameter unit 124 determines a HRV value for patient 14 based on, forexample, ventricular rate information received from electrical sensingmodule 86 and/or processor 80 (FIG. 3) (270). Similar to the activitylevel of patient 14, the HRV of patient 14 may be a daily (or otherperiod) value, e.g., the variability of a plurality of heart ratesdetermined over the course of a day. Similar to the activity level ofpatient 14, secondary parameter unit 124 may determine a median HRVvalue (MEDIAN_HRV) of patient 14 (272) as the median of the last “X”number of daily (or other period) HRV values. Secondary parameter unit124 may also determine a baseline HRV value

Comparison module 160 determines the ratio of the median HRV to abaseline HRV, and compares the ratio to a first threshold value(HRVfraction) and the median HRV to a second threshold value (minHRV)(274). The baseline HRV may be defined as the median HRV prior to thefluid index entering the threshold zone. The HRVfraction value may becomputed as a predetermined or variable fraction of the previous medianHRV, e.g., the median HRV prior to inclusion of the current daily value.When either condition is satisfied (“YES” branch of step 274),comparison module 160 sets the secondary parameter data equal to true(276). That is, when the median HRV value is less than HRVfraction orwhen the median HRV value is less than minHRV, comparison module 160sets the Boolean variable ACTIVITY_DATA equal to zero. However, whenboth conditions are not satisfied (“NO” branch of step 274), controllogic 178 sets the secondary parameter data value equal to false (278).In some examples, the analysis of HRV may include use of an HRV indexsimilar to the fluid index, which may accumulate over time as the medianHRV or ratio of median to baseline HRV is less than an adaptivethreshold, such as HRVfraction. The index may be compared to a thresholdto determine whether to set the secondary parameter data value to a trueor false value.

Diagnostic module 120 uses the secondary parameter data, e.g., theBoolean variable, to determine whether the secondary diagnosticparameters satisfy the predetermined condition (186 of FIG. 9 to detectworsening heart failure in patient 14. In some examples, diagnosticmodule 120 does not maintain a Boolean variable, but instead determineswhether the median activity level is less than one or more thresholds inresponse to determining that the fluid index is within the thresholdzone (182 and 184 of FIG. 9).

FIG. 15 is a flow diagram illustrating an example method for determiningwhether a patient is experiencing worsening heart failure based on thenight heart rate (NHR) of patient 14. Although illustrated with respectto night heart rate, this method may be similarly applied to othersecondary diagnostic parameters, such as the difference between day andnight heart rate, alone or in conjunction with NHR. In general, thedifference between day and night heart rate may satisfy a secondarydiagnostic parameter condition, and thereby indicated worsening heartfailure, when it is less than a threshold rate. The threshold may beabsolute, adaptive, or may involve multiple thresholds, which may beabsolute or adaptive.

With respect to NHR and the example of FIG. 15, initially, secondaryparameter unit 124 determines the NHR of patient 14 (280), e.g., basedon ventricular rate information received from electrical sensing module86 and/or processor 80 (FIG. 3) at night. The NHR of patient 14, similarto the activity level and HRV of patient 14, may be measured at periodicintervals throughout the night, and a daily (or other period) averagemay be determined. Secondary parameter unit 124 may determine a medianNHR value (MEDIAN_NHR) of patient 14 (282). The median value may bedetermined as the median of the last “X” number of daily (or otherperiod) NHR values.

Comparison module 160 determines the ratio of the median NHR to abaseline NHR, and compares the ratio to a first threshold (NHRdiff), andcompares the median NHR value to a second threshold value (maxNHR)(284). The baseline NHR may be defined as the median NHR prior to thefluid index entering the threshold zone. The NHRdiff value may be as anexample, 20 beats per minute, or any value that would represent aclinically significant increase in NHR. When either condition issatisfied (“YES” branch of step 274), comparison module 160 sets thesecondary parameter data equal to true (286). However, when bothconditions are not satisfied (“NO” branch of step 264), comparisonmodule 160 sets the secondary parameter data value equal to false (268).In some examples, the analysis of NHR may include use of an NHR indexsimilar to the fluid index, which may accumulate over time as the medianNHR or ratio of median to baseline NHR is greater than an adaptivethreshold. The index may be compared to a threshold to determine whetherto set the secondary parameter data value to a true or false value.

Diagnostic module 120 uses the secondary parameter data, e.g., theBoolean variable, to determine whether the secondary diagnosticparameters satisfy the predetermined condition (186 of FIG. 9 to detectworsening heart failure in patient 14. In some examples, diagnosticmodule 120 does not maintain a Boolean variable, but instead determineswhether the median activity level is less than one or more thresholds inresponse to determining that the fluid index is within the thresholdzone (182 and 184 of FIG. 9).

FIG. 16 is a graph illustrating an example of a fluid index 290 thatincrements over time relative to an example threshold zone. Asillustrated in FIG. 16, the threshold zone is defined by a higher andlower threshold (THRESH_HIGH and THRESH_LOW), e.g., as being between thethresholds. When fluid index 290 is within the threshold zone, e.g.,between the thresholds, as shown in FIG. 16, diagnostic module 120 looksto the one or more secondary diagnostic parameters to determine whetherthe patient is experiencing worsening heart failure.

FIG. 16 also illustrates a secondary diagnostic parameter monitoringthreshold 292, and an observation window 294. In some examples, an IMDor other device may begin monitoring secondary diagnostic parameterswhen the fluid index meets threshold 292, such that the observationwindow 294 includes some time prior to entry into the threshold zone. Inthis manner, the analysis of the secondary parameters may include dataprior to entry into the threshold zone, such as medians of secondarydiagnostic parameters prior to entry into the zone that may be used asbaselines, e.g., FIGS. 13-15.

FIG. 17 is a block diagram illustrating an example system 300 thatincludes an external device, such as a server 314, and one or morecomputing devices 316A-316N (“computing devices 316”) that are coupledto IMD 16 and programmer 24 shown in FIG. 1 via a network 312. In thisexample, IMD 16 may use its telemetry module 88 to communicate withprogrammer 24 via a first wireless connection, and to communication withan access point 310 via a second wireless connection. In the example ofFIG. 17, access point 310, programmer 24, server 314, and computingdevices 316A-216N are interconnected, and able to communicate with eachother, through network 312. In some cases, one or more of access point310, programmer 24, server 314, and computing devices 316A-316N may becoupled to network 312 through one or more wireless connections. IMD 16,programmer 24, server 314, and computing devices 316A-216N may eachcomprise one or more processors, such as one or more microprocessors,DSPs, ASICs, FPGAs, programmable logic circuitry, or the like, that mayperform various functions and operations, such as those describedherein. For example, as illustrated in FIG. 17, server 314 may compriseone or more processors 315 and an input/output device 313, which neednot be co-located.

Server 314 may, for example, monitor primary and secondary diagnosticparameters, e.g., based on signals or information received from IMD 16and/or programmer 24 via network 312, to detect worsening heart failureof patient 14 using any of the techniques described herein. Server 314may provide alerts relating to worsening heart failure of patient 16 vianetwork 312 to patient 14 via access point 310, or to one or moreclinicians via computing devices 316. In examples such as thosedescribed above in which IMD 16 and/or programmer 24 monitor the primaryand secondary diagnostic parameters, server 314 may receive an alertfrom the IMD or programmer via network 312, and provide alerts to one ormore clinicians via computing devices 316. Server 314 may generateweb-pages to provide alerts and information regarding the primary andsecondary diagnostic parameters, and may comprise a memory to storealerts and diagnostic or physiological parameter information for aplurality of patients.

Access point 310 may comprise a device that connects to network 312 viaany of a variety of connections, such as telephone dial-up, digitalsubscriber line (DSL), or cable modem connections. In other embodiments,access point 310 may be coupled to network 312 through different formsof connections, including wired or wireless connections. Network 312 maycomprise a local area network, wide area network, or global network,such as the Internet. System 300 may be implemented, in some aspects,with general network technology and functionality similar to thatprovided by the Medtronic CareLink® Network developed by Medtronic,Inc., of Minneapolis, Minn.

Additionally, using programmers 24, access points 310 or computingdevices 316, physicians and/or event patients may input clinicalinformation regarding the patients (such as symptoms, lab results,health care utilizations, etc.) that may be used as secondary parametersby the detection algorithm. Furthermore, the functionality describedherein with respect to monitoring worsening heart failure may beprovided by any one or more of the programmers 24, access points 310,server 314, or computing devices 316.

The techniques described in this disclosure, including those attributedto image IMD 16, programmer 24, or various constituent components, maybe implemented, at least in part, in hardware, software, firmware or anycombination thereof. For example, various aspects of the techniques maybe implemented within one or more processors, including one or moremicroprocessors, digital signal processors (DSPs), application specificintegrated circuits (ASICs), field programmable gate arrays (FPGAs), orany other equivalent integrated or discrete logic circuitry, as well asany combinations of such components, embodied in programmers, such asphysician or patient programmers, stimulators, image processing devicesor other devices. The term “processor” or “processing circuitry” maygenerally refer to any of the foregoing logic circuitry, alone or incombination with other logic circuitry, or any other equivalentcircuitry.

Such hardware, software, firmware may be implemented within the samedevice or within separate devices to support the various operations andfunctions described in this disclosure. In addition, any of thedescribed units, modules or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components, orintegrated within common or separate hardware or software components.

When implemented in software, the functionality ascribed to the systems,devices and techniques described in this disclosure may be embodied asinstructions on a computer-readable medium such as random access memory(RAM), read-only memory (ROM), non-volatile random access memory(NVRAM), electrically erasable programmable read-only memory (EEPROM),FLASH memory, magnetic data storage media, optical data storage media,or the like. The instructions may be executed to support one or moreaspects of the functionality described in this disclosure.

Various examples have been described. However, one of ordinary skill inthe art will appreciate that various modifications may be made to thedescribed examples without departing from the scope of the claims. Forexample, although described primarily with reference to intrathoracicimpedance, in some examples a cardiovascular pressure may additionallyor alternatively be used as a primary diagnostic parameter. In someexamples, a fluid index may increase based on increasing cardiovascularpressure over time, in a substantially similar manner to that which thefluid index discussed above increased based on decreasing intrathoracicimpedance over time. Examples of cardiovascular pressures that may bemonitored are right ventricular pressure, left atrial pressure, orestimated pulmonary artery diastolic pressure.

Furthermore, although described primarily with reference to examplesthat provide an alert in response to detecting worsening heart failure,other examples may additionally or alternatively automatically modify atherapy in response to detecting worsening heart failure in the patient.The therapy may be, as examples, a substance delivered by an implantablepump, cardiac resynchronization therapy, refractory period stimulation,or cardiac potentiation therapy. These and other examples are within thescope of the following claims.

1. A method comprising: monitoring at least one primary diagnosticparameter and at least one secondary diagnostic parameter of a patient,wherein the primary and secondary diagnostic parameters are associatedwith worsening heart failure; changing an index value over time based onthe first diagnostic parameter, wherein the index indicates worseningheart failure of the patient; determining whether worsening heartfailure is detected in the patient based on the fluid index when theindex is outside of a threshold zone defined by a lower threshold and anupper threshold; and determining whether worsening heart failure isdetected in the patient based on the secondary diagnostic parameter whenthe index is inside the threshold zone.
 2. The method of claim 1,wherein determining whether worsening heart failure is detected in thepatient based on the index when the index is outside a threshold zonecomprises: determining that worsening heart failure is detected in thepatient when the index is greater than the upper threshold value; anddetermining that worsening heart failure is not detected in the patientwhen the index is less than the lower threshold value.
 3. The method ofclaim 1, wherein monitoring at least one secondary diagnostic parametercomprises monitoring a plurality of secondary diagnostic parameters, andwherein determining whether worsening heart failure is detected in thepatient based on the secondary diagnostic parameter comprisesdetermining whether worsening heart failure is detected in the patientwhen any of the secondary diagnostic parameters indicates worseningheart failure.
 4. The method of claim 1, wherein the primary diagnosticparameter comprises intrathoracic impedance.
 5. The method of claim 1,wherein the primary diagnostic parameter comprises cardiovascularpressure.
 6. The method of claim 1, wherein the at least one secondarydiagnostic parameter comprises one or more of atrial fibrillation (AF)burden, ventricular rate during AF, ventricular fibrillation (VF)burden, ventricular rate during VF, atrial tachyarrhythmia (AT) burden,ventricular rate during AT, ventricular tachyarrhythmia burden (VT), orventricular rate during VT.
 7. The method of claim 1, wherein the atleast one secondary diagnostic parameter comprises one or more ofactivity level, heart rate variability, percentage of cardiacresynchronization pacing, night heart rate, difference between day heartrate and night heart rate, heart rate turbulence, heart ratedeceleration capacity, or baroreflex sensitivity.
 8. The method of claim1, wherein the at least one secondary diagnostic parameter comprises oneor more of respiratory rate, respiratory depth, or respiratory pattern.9. The method of claim 1, wherein the at least one secondary diagnosticparameter comprises one or more of weight, blood pressure, metrics ofrenal function, medication history, or history of heart failurehospitalization.
 10. The method of claim 1, wherein the threshold zoneis static over time.
 11. The method of claim 1, further comprisingchanging the threshold zone over time.
 12. The method of claim 11,wherein changing the threshold zone over time comprises at least one ofautomatically changing a size of the threshold zone, or automaticallychanging a range of the threshold zone.
 13. The method of claim 11,wherein dynamically changing the threshold zone comprises automaticallychanging the threshold zone as a function of time.
 14. The method ofclaim 1, wherein determining whether worsening heart failure is detectedin the patient based on the secondary diagnostic parameter comprisescomparing the secondary diagnostic parameter to a first threshold and asecond threshold, wherein the first threshold is a predeterminedconstant threshold, the second threshold is variable, and comparison ofthe secondary diagnostic parameter to the second threshold indicates arate of change of the secondary diagnostic parameter.
 15. The method ofclaim 1, further comprising generating an alert in response to detectingworsening heart failure in the patient.
 16. The method of claim 1,further comprising automatically modifying a therapy delivered to thepatient in response to detecting worsening heart failure in the patient.17. The method of claim 16, wherein the therapy comprises at least oneof a substance delivered by an implantable pump, cardiacresynchronization therapy, refractory period stimulation, or cardiacpotentiation therapy.
 18. The method of claim 1, wherein the indexcomprises a fluid index that indicates fluid accumulation of thepatient.
 19. The method of claim 1, wherein monitoring at least onesecondary diagnostic parameter of the patient comprises monitoring theat least one secondary diagnostic parameter when the index is greaterthan a secondary diagnostic parameter monitoring threshold that is lessthan the lower threshold.
 20. The method of claim 19, wherein monitoringat least one secondary diagnostic parameter of the patient comprisesmonitoring the at least one secondary diagnostic parameter when theindex is within an threshold zone defined by the secondary diagnosticparameter monitoring threshold and the upper threshold.
 21. A systemcomprising: at least one sensor; and a processor that: monitors at leastone primary diagnostic parameter and at least one secondary diagnosticparameter of a patient based on at least one signal from the at leastone sensor, wherein the primary and secondary diagnostic parameters areassociated with worsening heart failure of the patient, changes an indexvalue over time based on the primary diagnostic parameter, wherein theindex indicates worsening heart failure of the patient, determineswhether worsening heart failure is detected in the patient based on thefluid index when the index is outside of a threshold zone defined by alower threshold and an upper threshold, and determines whether worseningheart failure is detected in the patient based on the secondarydiagnostic parameter when the fluid index is inside the threshold zone.22. The system of claim 21, wherein the processor: determines thatworsening heart failure is detected in the patient when the index isgreater than the upper threshold value, and determines that worseningheart failure is not detected in the patient when the index is less thanthe lower threshold value.
 23. The system of claim 21, wherein theprocessor monitors a plurality of secondary diagnostic parameters, anddetermines whether worsening heart failure is detected in the patientwhen any of the secondary diagnostic parameters indicates worseningheart failure.
 24. The system of claim 21, wherein the at least onesensor comprises a plurality of electrodes, and the primary diagnosticparameter comprises intrathoracic impedance.
 25. The system of claim 21,wherein the at least one sensor comprises a pressure sensor, and theprimary diagnostic parameter comprises cardiovascular pressure.
 26. Thesystem of claim 21, wherein the at least one sensor comprises aplurality of electrodes, and the at least one secondary diagnosticparameter comprises one or more of atrial fibrillation (AF) burden,ventricular rate during AF, ventricular fibrillation (VF) burden,ventricular rate during VF, atrial tachyarrhythmia (AT) burden,ventricular rate during AT, ventricular tachyarrhythmia (VT), orventricular rate during VT.
 27. The system of claim 21, wherein the atleast one sensor comprises an accelerometer, and the at least onesecondary diagnostic parameter comprises activity level.
 28. The systemof claim 21, wherein the at least one sensor comprises a plurality ofelectrodes, and the at least one secondary diagnostic parametercomprises one or more of heart rate variability, night heart rate,difference between day heart rate and night heart rate, heart rateturbulence, or heart rate deceleration capacity.
 29. The system of claim21, wherein the at least one sensor comprises a plurality of electrodes,and the at least one secondary diagnostic parameter comprises one ormore of respiratory rate, respiratory depth, or respiratory pattern. 30.The system of claim 21, wherein the at least one secondary diagnosticparameter comprises one or more of percentage of cardiacresynchronization pacing, baroreflex sensitivity, weight, bloodpressure, metrics of renal function, medication history, or history ofheart failure hospitalization.
 31. The system of claim 21, wherein theat least one sensor comprises at least one electrode located on animplantable medical lead coupled to an implantable medical device. 32.The system of claim 21, wherein the at least one sensor is at least oneof within or coupled to an implantable medical device, and the processorcomprises a processor of the implantable medical device.
 33. The systemof claim 32, further comprising an external device that wirelesslycommunicates with the implantable medical device, wherein the processormonitors the at least one secondary parameter based on information inputby a user via the external device.
 34. The system of claim 21, whereinthe processor automatically changes the threshold zone as a function oftime.
 35. The system of claim 21, wherein the processor compares thesecondary diagnostic parameter to a first threshold and a secondthreshold, wherein the first threshold is a predetermined constantthreshold, the second threshold is variable, and comparison of thesecondary diagnostic parameter to the second threshold indicates a rateof change of the secondary diagnostic parameter.
 36. The system of claim21, wherein the processor provides an alert to a user in response todetecting worsening heart failure in the patient.
 37. The system ofclaim 21, further comprising an implantable medical device that deliversa therapy to the patient, wherein the processor automatically modifiesthe therapy in response to detecting worsening heart failure in thepatient.
 38. The system of claim 37, wherein the therapy comprises atleast one of a substance delivered by an implantable pump, cardiacresynchronization therapy, refractory period stimulation, or cardiacpotentiation therapy.
 39. The system of claim 21, wherein the indexcomprises a fluid index that indicates fluid accumulation of thepatient.
 40. The system of claim 21, wherein the processor monitors theat least one secondary diagnostic parameter when the index is greaterthan a secondary diagnostic parameter monitoring threshold that is lessthan the lower threshold.
 41. The system of claim 40, wherein theprocessor monitors the at least one secondary diagnostic parameter whenthe index is within a threshold zone defined by the secondary diagnosticparameter monitoring threshold and the upper threshold.
 42. Acomputer-readable medium comprising instructions that cause a processorto: monitor at least one primary diagnostic parameter and at least onesecondary diagnostic parameter of a patient, wherein the primary andsecondary diagnostic parameters are associated with worsening heartfailure; change an index value over time based on the primary diagnosticparameter, wherein the index indicates worsening heart failure of thepatient; determine whether worsening heart failure is detected in thepatient based on the index when the index is outside of a threshold zonedefined by a lower threshold and an upper threshold; and determinewhether worsening heart failure is detected in the patient based on thesecondary diagnostic parameter when the index is inside the thresholdzone.
 43. A system comprising: means for monitoring at least one primarydiagnostic parameter and at least one secondary diagnostic parameter ofa patient, wherein the primary and secondary diagnostic parameters areassociated with worsening heart failure; means for changing an indexvalue over time based on the primary diagnostic parameter, wherein theindex indicates worsening heart failure of the patient; means fordetermining whether worsening heart failure is detected in the patientbased on the index when the index is outside of a threshold zone definedby a lower threshold and an upper threshold; and means for determiningwhether worsening heart failure is detected in the patient based on thesecondary diagnostic parameter when the index is inside the thresholdzone.